Molecular Medicine: Department Directory

Laura Bohn

Laura Bohn Ph.D.

Chair And Professor, Department Of Molecular Medicine
Phone: (561) 228-2227
Mailing Address:
Location A235
130 SCRIPPS WAY BLDG 2A2
JUPITER FL 33458
Research Summary:

Research in the Bohn laboratory is focused on understanding how G protein-coupled receptors function in an endogenous setting to control physiologically relevant processes. We are most interested in receptors that mediate neurological functions, particularly those of the opioid, serotonin and cannabinoid families. Ultimately, our goal is to refine therapeutics- to enhance the benefits and eliminate the side effects. In this manner, we hope to inspire new approaches in treating pain, addiction and mood disorders.

The Bohn laboratory is most widely known for our work in opioid receptors. Early work while in the laboratory of Marc Caron and in collaboration with Robert Lefkowitz at Duke University indicated that barrestin2 plays a critical role in determining the physiological role of the mu opioid receptor (MOR) in vivo. Our laboratory has shown that barrestin2 plays different roles in regulating the MOR depending upon the physiological function assessed. This is very important as activation of the MOR results in multiple physiological processes ranging from the highly desirable suppression of pain perception to the deadly effects of respiratory failure. By determining which barrestin2-mediated signaling pathways are associated with these different physiological outcomes, we aim to elucidate a means to develop potent opioid analgesics that circumvent the adverse side effects. The bulk of our work to date suggests that if we preserve MOR coupling to G proteins, but eliminate the interactions between the receptor and the scaffolding protein, barrestin2, then we may be able to separate analgesic potency from constipation, respiratory suppression, tolerance and physical dependence.

Our lab is now focused on developing tool compounds that will allow us to test these hypotheses. Our agonists are designed, in collaboration with Dr. Tom Bannister of TSRI, to activate MOR in a manner that preserves or improves G protein signaling while eliminating the recruitment of barrestins. In addition to generating potential therapeutic leads, we are very interested in using these tools to elucidate MOR function in vivo. As we refine the pathways underlying different physiological responses, we will then know the signaling mechanisms to preserve and the ones to avoid.

We are also taking a similar approach with the kappa opioid receptors (KOR). The KOR in the midbrain acts to regulate dopamine and serotonin levels and thereby serves as an attractive target for modulating mood and reward thresholds. KOR ligands that display bias towards or against recruiting barrestins are of interest as barrestin2 has been implicated in facilitating aversive KOR-mediated behaviors. In our work with Dr. Jeff Aubé of Kansas University, we have been developing and evaluating KOR biased agonists to determine which physiologies are preserved or disrupted in mouse models. Since the KOR is involved in diverse physiological functions, compounds generated in this project may serve as interesting candidates for the treatment of depressive disorders and addiction. Moreover, KOR agonism produces antinociception and blocks itch and may also represent potential therapeutic avenues.

Recently, we have begun evaluating ligands for biased agonism among cannabinoid receptor (CB1 and CB2) agonists in collaboration with Dr. Alex Makriyannis at Northeastern University. Given the emerging implications for using cannabinoids as therapeutics for a wide-range of disorders, there are many opportunities for new drug development. This collaboration has also involved working with Dr. Ray Stevens (USC) and Dr. James Liu (Shanghai Tech) to solve the first crystal structures of antagonist and agonist bound CB1 receptors. Additional efforts in the laboratory focus on evaluating how antipsychotic drugs and mood altering neurotransmitters such as serotonin act at serotonin receptors.

Since the receptors described above are involved in modulating mood, motivation, and sensory perception, it stands to reason that our laboratory is most interested in developing means to treat pain, whether due to injury, disease or mental state, in a manner that adequately manages the pain, without causing deabilitating side effects.

Publications:
Grants:
  • Sep 2023 ACTIVE
    Drug Abuse and Addiction Research Programs
    SCRIPPS RESEARCH INST · Principal Investigator
  • Jun 2023 ACTIVE
    Deconvolution of Galbulimima bark pharmacology through chemical synthesis and target assignment
    SCRIPPS RESEARCH INST · Principal Investigator
  • Aug 2022 ACTIVE
    Molecular pharmacology of cannabinoid receptor probes
    NORTHEASTERN UNIV · Principal Investigator
  • Aug 2022 ACTIVE
    Biasing Mu Opioid Receptor Signaling in vivo
    NATL INST OF HLTH NIDA · Principal Investigator
  • Apr 2022 – Apr 2022
    Pharmacological interactions between conventional and biased MOR agonists
    NATL INST OF HLTH NIDA · Principal Investigator
  • Apr 2022 – Jun 2023
    Opioid Impacts on T Cell Pathways and Epigenetics to Modulate HIV Integration, Latency and Reservoirs
    UNIV OF CALIFORNIA SAN DIEGO · Principal Investigator
  • Apr 2022 – Aug 2023
    Structure and Function of CB2 Receptor
    NORTHEASTERN UNIV · Principal Investigator
  • Apr 2022 ACTIVE
    Synthesis and Evaluation of Functionally Biased Opioid Analgesics
    NATL INST OF HLTH NIDA · Principal Investigator
  • Apr 2022 ACTIVE
    Biased Kappa Opioid Agonists as Non-addictive Analgesics
    WAKE FOREST UNIV · Principal Investigator
Education:
  • 1999
    Ph.D. in Biochemistry & Molecular Biology
    Saint Louis University, School of Medicine
  • 1993
    Bachelor's of Arts in Chemistry
    Virginia Polytechnic Institute and State University
  • 1993
    Bachelor's of Science in Biochemistry
    Virginia Polytechnic Institute and State University
James Burke

James Burke

AST PROF
Phone: (561) 228-2784
Physical Address:
Location B211A
130 SCRIPPS WAY BLDG 2B2
JUPITER FL 33458
Publications:
Grants:
  • Sep 2023 ACTIVE
    Understanding the OAS/RNase L pathway during pathogenic viral infections
    NATL INST OF HLTH NIGMS · Principal Investigator
Education:
  • 2017-2022
    Postdoctoral Fellow
    University of Colorado Boulder
  • 2010-2016
    Ph.D.
    University of Texas at Austin
  • 2006-2009
    B.S. Biochemistry
    University of North Texas
Michael Cameron

Michael Cameron Ph.D.

Sr Scientific Director, Associate Professor Of Molecular Medicine, Department Of Molecular Medicine
Phone: (561) 228-2223
Mailing Address:
Location A201
130 SCRIPPS WAY BLDG 2A1
JUPITER FL 33458
Research Summary:

The Cameron Laboratory works on a variety of independent and collaborative projects centered on the metabolic fate of new chemical compounds. We explore the role of drug metabolism in chemical induced toxicity and drug-drug interactions. Current projects include evaluation of reactive metabolites and their role in drug induced toxicity, time and mechanism based inhibition of cytochrome P450, and the development of chemical tools to differentiate CYP3A4 and CYP3A5 activity in biological samples. The lab is also involved in several translational projects focused on the development of clinical candidates or molecular probes for the study of biological pathways. The lab offers Drug Metabolism and Pharmacokinetics (DMPK) expertise, collaborating with medicinal chemistry, biology and pharmacology groups. The lab evaluates such factors as chemical and metabolic stability, solubility, oral absorption, rat and mouse pharmacokinetics, tissue distribution, protein binding, P450 inhibition, reactive intermediate formation, and metabolite identification to help refine molecules. Current projects include optimization of neuropeptide Y Y2 receptor antagonists, orexin-1 receptor antagonists, (GABA) B receptor positive allosteric modulators, neurotensin 1 receptor agonists, a5* nicotinic acetylcholine receptors, positive allosteric modulators, kappa opioid receptor antagonists, and functionally biased mu opioid receptor agonists.

Publications:
Grants:
  • Apr 2024 ACTIVE
    Preclinical development of a precision therapy for a monogenic mental health disorder
    NATL INST OF HLTH · Co-Investigator
  • Jan 2024 ACTIVE
    An Innovative Approach to Identify Correctors of Metabolic Complications in HIV
    SCRIPPS RESEARCH INST · Co-Investigator
  • Sep 2023 ACTIVE
    Development of Clinical Candidates for the Treatment of Myotonic Dystrophy
    US ARMY MED RES ACQUISITION · Co-Investigator
  • Jul 2023 ACTIVE
    Synthesis of peripherally active CB1 agonists as analgesics
    WASHINGTON UNIV SAINT LOUIS · Principal Investigator
  • Sep 2022 ACTIVE
    Mitochondrial therapeutics for healthy brain aging
    NATL INST OF HLTH NIA · Co-Investigator
  • May 2022 ACTIVE
    Midwest AViDD Center – CORE C
    UNIV OF MINNESOTA · Co-Investigator
  • Apr 2022 – Aug 2022
    Mitochondrial therapeutics for healthy brain aging
    NATL INST OF HLTH NIA · Co-Investigator
  • Apr 2022 – Jun 2023
    Synthesis of peripherally active CB1 agonists as analgesics
    UNIV OF HLTH SCIENCES & PHARM ST LOUIS · Principal Investigator
  • Apr 2022 ACTIVE
    Identification of REV-ERB inverse agonists for cancer immunotherapy
    NATL INST OF HLTH NCI · Project Manager
  • Apr 2022 ACTIVE
    Synthesis and Evaluation of Functionally Biased Opioid Analgesics
    NATL INST OF HLTH NIDA · Co-Investigator
  • Apr 2022 ACTIVE
    Covalent Inhibition as a Method to Counteract Botulinum Intoxication
    SCRIPPS RESEARCH INST · Principal Investigator
  • Apr 2022 ACTIVE
    Development of novel therapeutics for opioid dependence
    ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · Project Manager
  • Apr 2022 ACTIVE
    Identification of small molecules for neurological complications of HIV and substance abuse comorbidity
    SCRIPPS RESEARCH INST · Co-Project Director/Principal Investigator
  • Apr 2022 ACTIVE
    Identification of novel anthelmintics through a target-based screen of a parasite ion channel
    MEDICAL COLLEGE OF WISCONSIN · Co-Investigator
Education:
  • 2000
    Ph.D. in Biochemistry
    Utah State University
  • 1994
    Bachelor's of Science in Chemistry
    Gonzaga University
Michalina Janiszewska

Michalina Janiszewska Ph.D.

Assistant Professor
Phone: (561) 228-2788
Mailing Address:
Location C251
130 SCRIPPS WAY BLDG 2C1
JUPITER FL 33458
Publications:
Grants:
  • Dec 2023 ACTIVE
    Scott R. MacKenzie Foundation Final Grant application (Janiszewska #230017)
    UF FOUNDATION · Principal Investigator
  • Jan 2022 ACTIVE
    American Cancer Society Institutional Research Grant
    AMERICAN CANCER SOCIETY · Project Manager
Education:
  • 2012
    Ph.D. in Life Sciences
    University of Lausanne
  • 2007
    Master's of Science in Medical Biotechnology
    University of Wroclaw
  • 2005
    Bachelor's of Science in Biotechnology
    University of Wroclaw
Donald G Phinney

Donald G Phinney Ph.D.

Professor
Phone: (561) 228-2214
Mailing Address:
Location A215
130 SCRIPPS WAY BLDG 2A2
JUPITER FL 33458

Dr. Phinney received his B.A. in Chemistry and Mathematics from the University of Vermont and a Ph.D. in Biochemistry from Temple University School of Medicine in Philadelphia. He then completed his post-doctoral studies at the Fox Chase Cancer Center where he was awarded an American Cancer Society Fellowship to examine the transcriptional regulation of the JunB oncogene. Dr. Phinney then spent nine years at Tulane University Health Sciences Center where he advanced through the ranks to Professor of Immunology and Microbiology and Associate Director of Research for the Center for Gene Therapy. He joined Scripps Florida in 2009 and is currently a Professor in the Department of Molecular Medicine.

Research Summary:

The Phinney lab combines basic and translational research and drug discovery to deliver highly efficacious cell-based and drug-based therapies for the treatment of skeletal-related pathologies and cancer. Currently the lab is pursuing several different areas of investigation to achieve these goals. One area of focus is directed at enhancing the potency and improving the efficacy of mesenchymal stem cell (MSC)-based therapies, which are widely used in regenerative medicine for the treatment of ischemic and immune-related diseases. These efforts have culminated in the development of a Clinical Indications Prediction (CLIP) Scale that may be used to develop MSC-based therapies tailored to specific disease indications. Ongoing work is directed at validating the CLIP scale and expanding its range of applications. Another area of focus is directed at understanding the molecular mechanism that drive skeletal pathology in response to diet-induced obesity, mechanical unloading (disuse), and chronological aging using mouse models. In these studies, emphasis is on evaluating how these conditions impact the frequency and function of nice resident skeletal stem cells in bone marrow and developing therapeutics to preserve bone integrity. Lastly, the laboratory is also pursuing development of small molecule therapeutics to augment the efficacy and reduce the toxicity of existing chemotherapeutics and immuno-therapies for treating breast cancer.

Publications:
Grants:
  • Mar 2024 ACTIVE
    A Clinical Indications Prediction (CLIP) Scale for Human Mesenchymal Stem Cells
    NATL INST OF HLTH NHLBI · Principal Investigator
  • Sep 2022 ACTIVE
    Tissue Selective Glucocorticoids
    NATL INST OF HLTH NIGMS · Co-Investigator
  • Aug 2022 ACTIVE
    A novel miR-544 targeting small molecule as an adjuvant therapy for preventing breast cancer metastasis and relapse
    US ARMY MED RES ACQUISITION · Principal Investigator
  • Apr 2022 – Feb 2024
    A Clinical Indications Prediction (CLIP) Scale for Human Mesenchymal Stem Cells
    NATL INST OF HLTH NHLBI · Principal Investigator
Education:
  • 1990
    Ph.D. in Biochemistry
    Temple University, School of Medicine
  • 1984
    Bachelor's of Arts in Chemistry and Mathematics
    The University of Vermont
Thomas Bannister

Thomas Bannister Ph.D.

Research Professor (Sr. Scientific Director), Department Of Molecular Medicine
Phone: (561) 228-2206
Mailing Address:
Location A229
130 SCRIPPS WAY BLDG 2A2
Jupiter FL 33458
Physical Address:
Location A229
130 SCRIPPS WAY BLDG 2A2
Jupiter FL 33458
Research Summary:

Organic/Medicinal Chemistry and Drug Discovery

The discovery of possible drug candidates is a highly collaborative endeavor, with medicinal chemistry as a core, problem-solving component. My major research efforts are joint projects with world experts in cancer biology and neuroscience, wherein my group provides the organic and medicinal chemistry expertise and drug design insights. In general, we strive to find novel ways to target poorly-treated, common, and devastating disorders that increasingly burden world health care systems.

Neuroscience studies include:

— Biased mu opioid agonists, aiming for a holy grail of sorts: to separate the robust pain relief –provided by opiates from their many unwanted side effects. This collaboration with Laura Bohn’s group has led to findings published in 2017 in Cell, with follow-up chemistry disclosure in the Journal of Medicinal Chemistry in late 2018 (featured on the cover). — NOP agonists, for post-traumatic stress disorder (PTSD) and alcohol addiction relapse therapy. — NAD-elevating neuroprotectants, for Alzheimer’s and Parkinson’s Diseases, and for ALS.

Cancer projects include:

— KLF5 inhibitors for colorectal cancer therapy. — TBK1 and IKKi dual kinase inhibitors, for hormone-refractory prostate cancer. — Inhibitors of kinases CK1delta, ASK1, and ULK1, for various cancers. — Modulators of the HIPPO-YAP pathway, for various cancers. — Other exploratory efforts include:

High-throughput screening-based “chemical probe development”, seeking first-in-class small molecules for investigating the therapeutic potential of new target proteins. Probe development efforts encompass multiple therapeutic areas, including treatments for cancers, glaucoma, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), addiction, infectious diseases, and mood disorders. One chemical probe effort targets the orphan GPCR GPR151, a target that may be relevant for the development of treatments for addiction, depression, and schizophrenia.The discovery of possible drug candidates is a highly collaborative endeavor, with medicinal chemistry as a core, problem-solving component. Our major efforts are thus joint projects with world experts in cancer biology and neuroscience, wherein our group provides the organic and medicinal chemistry expertise.

Our cancer projects target unique metabolic phenotypes of tumor cells, identifying defining molecular characteristics to be exploited for the development of targeted therapies. Most tumor types have a shared reliance upon active transport of nutrients and building blocks to drive rapid cancer cell growth and to sustain survival. They also largely rely upon glycolysis for ATP production (the Warburg effect). As examples, we have created molecules to keep tumor cells from exporting lactate, the end product of glycolysis. We have also designed compounds to block amino acid transporters that are up-regulated by many tumors. We have a program targeting expression of a transcription factor that drives colon cancer progression. We also have a number of kinase inhibitor programs aimed the discovery of treatments for brain cancers, triple-negative breast cancer, hormone-resistant prostate cancer, and perhaps other forms as well. This are collaborative efforts with top TSRI cancer biologists including Derek Duckett, Joseph Kissil, Jun-li Luo, and also including John Cleveland from the Moffitt Cancer Center.

Many of our anticancer programs have a computational chemistry-directed focus, relying on molecular modeling based upon published coordinates, virtual screening, scoring, and validation of predicted hits through chemical synthesis. We use the Schrodinger suite of modeling software in these studies. For future work we may have a need to hire postdoctoral scientists with both computational and synthesis experience. Please contact me for further information.

In our neuroscience studies we are developing GPCR agonists that have targeted effects in the brain. We are exploring GPCR signaling bias in mu opioid receptor activation, aiming for a holy grail of sorts: to separate the robust pain relief provided by opiates from their many unwanted side effects. This collaboration with Laura Bohn’s group has led to pain relievers that seem to be devoid of many of the side effects of morphine and related opiates, such as respiratory suppression, heart rate effects, and GI effects (constipation). In a separate study we identified tool compound with promise in an animal model of post-traumatic stress disorder (PTSD).

Other exploratory efforts use medicinal chemistry in concert with high-throughput screening or following HTS campaigns, where we seek to discover and optimize “chemical probes”, or first-in-class small molecules that should prove useful for investigating the therapeutic potential of new target proteins. Such probe development efforts encompass multiple therapeutic areas, including treatments for ALS, Parkinson’s Disease, addiction, infectious diseases, cancers, glaucoma, and mood disorders.

One such chemical probe effort, a collaboration with Patsy McDonald, targets the orphan GPCR GPR151, a target that may be relevant for the development of treatments for addiction, depression, and schizophrenia. In a collaboration with Sathya Puthanveettil we are investigating the potential of facilitating the function of kinesin motor proteins as a novel approach to therapies for Alzheimer’s disease (AD) and frontal temporal dementia (FTD), which are poorly-treated, common, and devastating disorders that increasingly burden world health care systems. In a collaboration with Corinne Lasmezas, we are developing compounds that rescue neurons from toxicity of protein aggregates, relevant for developing new therapies for ALS and Parkinson’s Disease.

As you can tell, collaborative drug discovery research is order of the day in my lab!

Members of my group benefit from interactions not only with other chemists but with top biologists and pharmacologists, as they partake in project team meetings as well as in our weekly chemistry group meetings. My research is funded currently by 8 NIH grants on which I am a co-principal investigator and 8 others NIH grants where I am a named investigator or co-investigator.

On occasion I have openings for outstanding postdoctoral fellows in my labs. As mentioned above, an especially good fit would be a postdoc with lab synthesis experience and with prior expertise in using the Schrodinger suite of molecular modeling software, to aid our virtual screening-based efforts. Our postdoctoral scientists collaborate with a team of biological co-investigators, applying knowledge and experience in modern organic, heterocyclic, and/or medicinal chemistry toward an ongoing drug discovery effort. Excellent communication skills, good synthetic organic chemistry laboratory skills, ability to work in the US, and familiarity with modern synthetic techniques and instrumentation are required in this role. Contact me for further details.

Publications:
Grants:
  • Jan 2024 ACTIVE
    An Innovative Approach to Identify Correctors of Metabolic Complications in HIV
    SCRIPPS RESEARCH INST · Co-Investigator
  • Apr 2023 ACTIVE
    Preclinical Studies for the Therapeutic Development of a Novel Neuroprotectant for ALS
    US ARMY MED RES ACQUISITION · Co-Investigator
  • Aug 2022 ACTIVE
    Biasing Mu Opioid Receptor Signaling in vivo
    NATL INST OF HLTH NIDA · Co-Investigator
  • May 2022 ACTIVE
    Midwest AViDD Center – Project 5
    UNIV OF MINNESOTA · Principal Investigator
  • May 2022 ACTIVE
    Midwest AViDD Center – CORE C
    UNIV OF MINNESOTA · Principal Investigator
  • Apr 2022 – Nov 2023
    Therapeutic Targeting of Casein Kinase-1-delta in Primary Metastatic Breast Cancer
    H LEE MOFFITT CANCER CTR & RES INST · Principal Investigator
  • Apr 2022 ACTIVE
    Synthesis and Evaluation of Functionally Biased Opioid Analgesics
    NATL INST OF HLTH NIDA · Principal Investigator
  • Apr 2022 ACTIVE
    Development of New Casein Kinase 1 Inhibitor for the Treatment of Brain Cancers
    H LEE MOFFITT CANCER CTR & RES INST · Principal Investigator
  • Apr 2022 ACTIVE
    Identification of novel anthelmintics through a target-based screen of a parasite ion channel
    MEDICAL COLLEGE OF WISCONSIN · Co-Investigator
  • Apr 2022 ACTIVE
    Identification of small molecules for neurological complications of HIV and substance abuse comorbidity
    SCRIPPS RESEARCH INST · Co-Project Director/Principal Investigator
Education:
  • 1991
    Ph.D. in Organic Chemistry
    Indiana University
  • 1987
    Master's of Philosophy
    Yale University
  • 1986
    Master of Science
    Yale University
  • 1984
    A.B. in Chemistry
    Wabash College
Ezgi Hacisuleyman

Ezgi Hacisuleyman

Assistant Professor
Phone: (561) 228-3505
Physical Address:
130 SCRIPPS WAY # 3B2
JUPITER FL 33458
Education:
  • 2010-2015
    Ph.D. in Molecular Biology and Biochemistry
    Harvard University
  • 2006-2010
    Bachelor of Engineering, Chemical Engineering
    Massachusetts Institute of Technology
  • 2006-2010
    Bachelor of Science, Molecular Biology and Genetics
    Massachusetts Institute of Technology
Theodore Kamenecka

Theodore Kamenecka Ph.D.

Sr. Scientific Director, Department Of Molecular Medicine
Phone: (561) 228-2207
Mailing Address:
Location A207
130 SCRIPPS WAY BLDG 2A2
JUPITER FL 33458
Physical Address:
Room A230
110 Scripps Way
Jupiter FL 33458
Research Summary:

Medicinal Chemistry and Drug Discovery

The research interest in my group is in the design, synthesis and evaluation of novel compounds of biological and therapeutic interest. Currently, we are involved in the design and synthesis of novel small molecule modulators of nuclear receptors, GPCR’s, ion channels, kinases and mitochondria for the therapeutic treatment of addiction, diabetes and obesity, multiple sclerosis, cognitive health and aging. Working closely with other departments such as molecular biology, pharmacology, and drug metabolism, we optimize lead compounds for potency, ADME (absorption, distribution, metabolism, and excretion), safety pharmacology, and toxicology in order to generate compounds suitable for preclinical development.

Publications:
Grants:
  • Apr 2024 ACTIVE
    Preclinical development of a precision therapy for a monogenic mental health disorder
    NATL INST OF HLTH · Principal Investigator
  • Apr 2024 ACTIVE
    Ligand and transcriptional regulation of the nuclear receptor RORa on TH17 cell development and inflammation
    NATL INST OF HLTH NIDDK · Co-Investigator
  • Mar 2024 ACTIVE
    Optimization of SR1903 and 10171
    SYNKINE THERAPEUTICS · Co-Investigator
  • Jul 2023 ACTIVE
    Understanding the role of RORa in T-cell mediated colitis
    CROHNS & COLITIS FOUNDATION · Other
  • Apr 2023 ACTIVE
    Molecular basis of activation of the orphan nuclear receptor Nurr1
    VANDERBILT UNIVERSITY · Co-Investigator
  • Apr 2023 ACTIVE
    Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for Glioblastoma
    NATL INST OF HLTH NINDS · Principal Investigator
  • Mar 2023 ACTIVE
    Ligand-dependent regulation of the nuclear receptor REV-ERBa in TH17 cell development and inflammation
    NATL INST OF HLTH NIDDK · Co-Investigator
  • Mar 2023 ACTIVE
    Mechanistic studies of corepressor-mediated PPAR? transcriptional repression
    VANDERBILT UNIVERSITY · Co-Project Director/Principal Investigator
  • Mar 2023 ACTIVE
    Demo batch scale-up of MT-125
    MYOSIN THERAPEUTICS · Principal Investigator
  • Sep 2022 ACTIVE
    Mitochondrial therapeutics for healthy brain aging
    NATL INST OF HLTH NIA · Co-Investigator
  • Sep 2022 ACTIVE
    Tissue Selective Glucocorticoids
    NATL INST OF HLTH NIGMS · Co-Investigator
  • Apr 2022 ACTIVE
    Targeting Go and Grow in Glioblastoma
    MAYO CLINIC · Co-Investigator
  • Apr 2022 ACTIVE
    Small molecules targeting hepatic glucose production and insulin resistance
    DANA FARBER CANCER INST · Co-Investigator
  • Apr 2022 ACTIVE
    Development of novel therapeutics for opioid dependence
    ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · Principal Investigator
  • Apr 2022 ACTIVE
    Targeting Cellular Senescence to Extend Healthspan
    MAYO CLINIC · Principal Investigator
  • Apr 2022 ACTIVE
    Identification of REV-ERB inverse agonists for cancer immunotherapy
    NATL INST OF HLTH NCI · Co-Investigator
  • Apr 2022 – Mar 2023
    Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for Glioblastoma
    NATL INST OF HLTH NINDS · Principal Investigator
  • Apr 2022 – Feb 2023
    Mechanistic studies of corepressor-mediated PPAR? transcriptional repression
    NATL INST OF HLTH NIDDK · Co-Investigator
  • Apr 2022 – Feb 2023
    Molecular basis of activation of the orphan nuclear receptor Nurr1
    NATL INST OF HLTH NIA · Co-Investigator
  • Apr 2022 – Sep 2022
    Parallel Multimodal High-throughput screening to identify activators of the orexin receptors
    NATL INST OF HLTH NIMH · Principal Investigator
  • Apr 2022 – Aug 2022
    Mitochondrial therapeutics for healthy brain aging
    NATL INST OF HLTH NIA · Co-Investigator
  • Apr 2022 – Jul 2022
    Optimization of SR1903 and SR10171
    SYNKINE THERAPEUTICS · Co-Project Director/Principal Investigator
  • Apr 2022 – Jun 2022
    ALDH1a1 Inhibition As A Therapeutic Target In Visceral Adiposity and Type 2 Diabetes
    BRIGHAM AND WOMENS HOSPITAL · Co-Project Director/Principal Investigator
  • Apr 2022 ACTIVE
    Developing nonmuscle myosin II inhibitors for the treatment of glioblastoma
    NATL INST OF HLTH NINDS · Co-Investigator
  • Apr 2022 – May 2022
    Identification of Chemical Probes for the Orphan Nuclear Receptor NR2F6
    NATL INST OF HLTH NCI · Co-Investigator
Education:
  • 1996-1998
    Post-doctorate
    Memorial Sloan Kettering Cancer Center
  • 1990-1996
    Ph.D. in Chemistry
    University of California, Irvine
  • 1986-1990
    Bachelor of Science in Chemistry
    University of Rochester
Patrick Griffin

Patrick Griffin Ph.D.

Scientific Director And Professor
Phone: (561) 228-2200
Mailing Address:
Location A223
130 SCRIPPS WAY BLDG 2A2
JUPITER FL 33458

My scientific career has focused on the study of protein structure and approaches to modulating protein function via synthetic small molecules with a focus on nuclear receptors. I have a broad background in drug discovery and development that spans the last 25+ years. I received a Ph.D. in Chemistry from the University of Virginia under the direction of Professor Donald F. Hunt where I was involved in methodology development in the field of Biological Mass Spectrometry. After graduating from UVa, I was a Postdoctoral Fellow for Professor Leroy Hood at Caltech where I was involved in the application of mass spectrometry to systems biology.

Prior to Scripps, I was Chief Science Officer of ExSAR Corporation, NJ, a biotech company focused the use of HDX mass spectrometry (HDX-MS) to aid in the development of chemical chaperones for protein misfolding disorders. Prior to ExSAR, I was Senior Director, Chemistry, at Merck Research Laboratories where he spent over 11 years applying biological mass spectrometry and proteomics to a wide range of therapeutic areas including metabolic disorders, cardiovascular disease, and infectious diseases. At Merck, I headed the discovery DMPK operation within the Chemistry Department and the Molecular Profiling Proteomics group. My team made significant contributions to over 35 safety assessment programs. Most significant were my team’s contributions towards the discovery and development of MK-0431, a DPP4 inhibitor now in clinical use (Januvia), and towards clinical development of DMP-777, an elastase inhibitor for treatment of cystic fibrosis that progressed to phase IIb trials.

In 2004, I joined The Scripps Research Institute (TSRI) Scripps Florida as Professor and in 2007 was named Professor and founding Chair of the Department of Molecular Therapeutics. As PI, Co-PI, and co-investigator on several NIH-funded grants, my research continues to focus on protein structure and function, particularly on mutational- and ligand-mediated alterations in protein structural plasticity, as well as quantitative SAR to facilitate lead optimization of molecules targeting therapeutic proteins. Using mutagenesis, HDX-MS, crystallography, proteomics and genomics my research is focused on structure-function of nuclear receptors, enzymes, and G protein coupled receptors (GPCRs). My research program has a major focus on understanding nuclear receptor (NR) signaling using structural, chemical and biological approaches. We have made significant contributions to understanding the mechanism of ligand activation of NRs such as PPARs, RORs, REV-ERBs, LRH1, VDR, ER, GR, and PR. We have also made significant contributions dissecting domain-domain interactions in control of positive and negative allostery. Our chemical biology program is focused on the RORs, PPARs, VDR and LRH1. In each of these programs we are developing functionally selective and promoter-specific modulators targeting disease such as cancer, autoimmune, obesity, and diabetes. My lab is well known for the development and application of biophysical methods including our HDX and XL-MS platform for the analysis of protein plasticity with a focus on NRs, enzymes, and GPCRs.

For the first half of my career I was in industry where there was less of an emphasis on publications. However, over the last 16 years as an academic I have published >240 peer-reviewed manuscripts. According to Google Scholar I have an h-index of 83 (58 since 2016) and an i10-index of 223. Below is a URL for My Bibliography of Patrick R. Griffin; some papers are under Griffin P.

Research Summary:

As a graduate student at the University of Virginia, I worked in Don Hunt’s lab alongside John Yates and together we performed ground-breaking studies in the use of mass spectrometry to determine the primary structure of proteins. I am first author on a paper describing the complete sequence of a protein using tandem mass spectrometry. Prior, only a few small proteins for which their amino sequence was known had been sequenced by tandem mass spectrometry. This work helped validate that it was possible to sequence proteins using tandem mass spectrometry. I am first author on one of the first papers describing the using low nano-LC coupled with ESI. I contributed to many other publications demonstrating the use of mass spectrometry for structural analysis of proteins.

While at Merck Research Laboratories, my lab made significant contributions to a wide range of projects including key contributions to the development of the DPP4 program which led to the approval and marketing of Januiva. The range of contributions to drug discovery and development are exemplified in manuscripts listed below. My efforts in drug discovery have continued in the academic setting.

In 2002 I became interested in the application of hydrogen/deuterium exchange mass spectrometry. My lab focused on the development of a fully automated system, advanced software to facilitate robust high precision analysis, and applications of HDX in protein-ligand interactions with an emphasis on nuclear receptors, enzymes, and GPCRs. The publications listed below include an extensive list of key contributions to the HDX field.

In addition to the advancement of structural proteomics, my research has focused on chemical biology approaches to better understand nuclear receptor signaling. Our group described the first synthetic ligand for the orphan nuclear receptor NR1F subfamily (ROR)s and subsequently showed the utility of advanced compounds as anti-inflammatory and anti-obesity agents as well as RORG agonists for enhancing protective immunity in the context of cancer therapy. Our lab has also contributed to a fundamentally new understanding of the mechanism by which the nuclear receptor PPARG impacts insulin sensitivity.

Highlights on grant funding related to drug development programs

• I was consortium PI of the “The Comprehensive Center for Chemical Probe Discovery and Optimization at Scripps,” I had both a leadership role and a scientific role on this large multi-center 6-year U54 MLPCN Roadmap initiative.

• I was consortium PI of a RC4 program in collaboration with Bruce Spiegelman at the Dana Faber, I was involved in the discovery and development of novel molecules for the treatment of obesity and diabetes. Work from our labs in this area led us to co-found Ember, a private biotech funded by Third Rock Ventures.

• I was Co-PI on a NIDA funded U19 NCDDDG focused on the discovery and development of novel positive allosteric modulators of GABAB receptor for treatment of nicotine addiction.

• I served on the Scripps-Pfizer collaboration Steering Committee for its 5 year term coordinating collaborative drug discovery programs.

• I am PI of a 13-year long collaboration between my lab and Eli Lilly. • I am PI on a collaborative grant with the private Biotech Synkine Therapeutics.

• I am Co-PI on a NIH Blueprint UH3 titled, “Developing nonmuscle myosin II inhibitors for substance use relapse.” Co-founder of Myosin Therapeutics. The Myosin Therapeutics’ clinical candidate emerged from the NIH Blueprint program.

Publications:
Grants:
  • Apr 2024 ACTIVE
    Defining the Transcriptional Activity of NR2F6 in TH17 cells
    NATL INST OF HLTH NIDDK · Other
  • Mar 2024 ACTIVE
    Optimization of SR1903 and 10171
    SYNKINE THERAPEUTICS · Principal Investigator
  • May 2023 ACTIVE
    Architecture of inhibitory G protein signaling in the hippocampus
    UNIV OF MINNESOTA · Co-Investigator
  • Apr 2023 ACTIVE
    Molecular basis of activation of the orphan nuclear receptor Nurr1
    VANDERBILT UNIVERSITY · Principal Investigator
  • Apr 2023 ACTIVE
    Probing SNARE assembly and disassembly in vitro and in live cells
    NATL INST OF HLTH NIGMS · Other
  • Apr 2023 – Mar 2024
    Behavior of HIV in Viral Environments (B-HIVE) 2023
    SEATTLE CHILDRENS HOSPITAL · Principal Investigator
  • Mar 2023 ACTIVE
    Mechanistic studies of corepressor-mediated PPAR? transcriptional repression
    VANDERBILT UNIVERSITY · Principal Investigator
  • Feb 2023 – Feb 2023
    Molecular mechanism of PIN1-mediated regulation of the nuclear receptor PPAR?
    NATL INST OF HLTH NIDDK · Other
  • Jan 2023 ACTIVE
    Elucidating transsynaptic regulation of metabotropic glutamate receptors
    NATL INST OF HLTH NINDS · Other
  • Nov 2022 ACTIVE
    Structural Biology of Connexin Membrane Channels
    UNIV OF MIAMI · Principal Investigator
  • Sep 2022 ACTIVE
    Quantifying and modeling ligand-dependent control of RORy dynamics via structural proteomics
    NATL INST OF HLTH NIDDK · Principal Investigator
  • Jun 2022 – Mar 2023
    Behavior of HIV in Viral Environments (B-HIVE)
    SEATTLE CHILDRENS HOSPITAL · Principal Investigator
  • May 2022 ACTIVE
    Structural dynamics of progesterone receptor-coactivator complexes
    NATL INST OF HLTH NCI · Principal Investigator
  • Apr 2022 ACTIVE
    Roles of HIV-1 capsid-binding FG-motif containing cellular cofactors in infection
    UNIV OF COLORADO DENVER & ANSCHUTZ MED · Principal Investigator
  • Apr 2022 ACTIVE
    Ultra-potent HIV capsid inhibitors
    UNIV OF COLORADO DENVER & ANSCHUTZ MED · Principal Investigator
  • Apr 2022 ACTIVE
    Chemistry and Biology of ADP-Ribosylation-Dependent Signaling
    UNIV OF SOUTHERN CALIFORNIA · Principal Investigator
  • Apr 2022 ACTIVE
    Small molecules targeting hepatic glucose production and insulin resistance
    DANA FARBER CANCER INST · Principal Investigator
  • Apr 2022 ACTIVE
    Developing nonmuscle myosin II inhibitors for the treatment of glioblastoma
    NATL INST OF HLTH NINDS · Co-Investigator
  • Apr 2022 ACTIVE
    Mechanistic analysis of therapeutic targets using hydrogen/deuterium exchange mass spectrometry (HDX MS)
    ELI LILLY AND CO · Principal Investigator
  • Apr 2022 – Feb 2023
    Mechanistic studies of corepressor-mediated PPAR? transcriptional repression
    NATL INST OF HLTH NIDDK · Co-Investigator
  • Apr 2022 – Feb 2023
    Molecular basis of activation of the orphan nuclear receptor Nurr1
    NATL INST OF HLTH NIA · Co-Investigator
  • Apr 2022 – Oct 2022
    Structural Biology of Connexin Membrane Channels
    UNIV OF VIRGINIA · Principal Investigator
  • Apr 2022 – Aug 2022
    Developing chemoproteomic approaches to decipher the regulatory network of LRH-1,a nuclear receptor implicated in hepatic metabolism
    NATL INST OF HLTH NIDDK · Principal Investigator
  • Apr 2022 – Aug 2022
    HIV Interactions in Viral Evolution
    SEATTLE CHILDRENS HOSPITAL · Principal Investigator
  • Apr 2022 – Jul 2022
    Optimization of SR1903 and SR10171
    SYNKINE THERAPEUTICS · Principal Investigator
  • Apr 2022 ACTIVE
    PPARG regulates osteocyte bioenergetics and function during aging
    UNIV OF TOLEDO · Principal Investigator
  • Apr 2022 – Jun 2022
    ALDH1a1 Inhibition As A Therapeutic Target In Visceral Adiposity and Type 2 Diabetes
    BRIGHAM AND WOMENS HOSPITAL · Principal Investigator
Education:
  • 1989
    Ph.D. in Chemistry
    University of Virginia
  • 1985
    Bachelor's of Science in Chemistry
    Syracuse University
Scott Hansen

Scott Hansen Ph.D.

Associate Professor Of Department Of Molecular Medicine
Phone: (561) 228-2415
Mailing Address:
Location C260
130 SCRIPPS WAY BLDG 2C1
JUPITER FL 33458
Research Summary:

Our laboratory studies the role of cholesterol in setting thresholds of anesthesia, mechanosensation, amyloid formation, and viral entry. In each area of research, we study how cholesterol controls the threshold that regulates biological function and the severity of disease. By understanding the thresholds, we aim to treat diseases caused by altered cholesterol levels and signaling lipids.

Anesthesia: For hundred years scientist believed that membrane lipids were involved in the anesthesia (reversible loss of consciousness). At the heart of the question was the following, How can disrupting a lipid membrane activate or inhibit and ion channel? We have shown that anesthetics disrupt compartmentalization of signaling molecules in cholesterol dependent lipid compartments. The anesthetics counteract cholesterol causing the proteins to escape and activate an ion channel. This established at least one clear molecular mechanism for the membrane as a target of inhaled anesthetics. We are studying this mechanism for additional ion channels that mediate anesthesia in people.

Pain threshold (mechanosensation): We have shown mechanical force disrupts cholesterol dependent compartmentalization of proteins, similar to anesthetics. In addition to defining a novel mechanosensation pathway, we are developing potential therapeutic compounds that will activate an analgesic channel downstream of mu opioid receptor. We aim to develop therapeutics that will have similar pain reducing benefits as opioids, but without the addiction.

Viral entry: We have recently proposed a model for cholesterol dependent SARS-COV-2 viral infectivity, based on our understanding of cholesterol mediated membrane protein translocation. As cholesterol increases the ability of the virus to enter the cell increases. Increased viral entry increases inflammation, which in turn increases cholesterol and more viral entry. We are currently studying cholesterol loading in lung tissues in aged animals.

Publications:
Grants:
  • Jan 2024 ACTIVE
    Molecular basis for cholesterol regulation of Kir2.1 in cardiac arrhythmia
    AMER HEART ASSOCIATION · Other
  • Sep 2022 ACTIVE
    Regulation of amyloid production by focused ultrasound
    NATL INST OF HLTH NIA · Principal Investigator
  • Apr 2022 ACTIVE
    The role of lipid raft disruption in the activation of TREK-1 channels by anesthetics
    NATL INST OF HLTH NINDS · Principal Investigator
Education:
  • 2006
    Ph.D.
    University of California, San Diego
  • 1999
    Bachelor's of Science in Chemistry
    Utah State University
Claudio A Joazeiro

Claudio A Joazeiro Ph.D.

Professor
Phone: (561) 228-3211
Mailing Address:
Location C238
130 SCRIPPS WAY BLDG 2C1
Jupiter FL 33458

website: www.joazeirolab.com

Research Summary:

See lab website: www.joazeirolab.com

Role of the ubiquitin-proteasome system in cellular regulation and disease

E3 ubiquitin ligases are the components that confer specificity to the ubiquitin system. Consistent with their critical role in cellular regulation, mutations affecting E3s can cause human disease—as illustrated by the cases of BRCA1 in breast cancer and of Parkin in Parkinsonism. Our laboratory is engaged in three main areas of research related to E3s:

1] We are interested in elucidating E3s’ function and mechanisms. For this purpose, we utilize cell and molecular biology approaches with mammalian cells, mice and yeast; our expertise is complemented by close collaborations on structural biology, bioinformatics, mass spectrometry, next-generation sequencing, and fly models;

2]We utilize the information we learn from the above studies to develop assays that are amenable to high-throughput screening, which are then used to identify small molecule inhibitors of E3 ligases. Such compounds can then be both turned into tools to interrogate biology, and developed as pharmaceutical drug candidates;

3] We collaborate with clinicians to translate our basic research findings into therapeutically-relevant discoveries.

Research Interests:
  • Microbiology
  • Molecular therapy
  • Neurodegenerative diseases
  • Protein biochemistry
  • RNA binding proteins
  • Rare neuromuscular disorders
  • Small molecule drug discovery
Publications:
Grants:
  • Jun 2022 ACTIVE
    POLYALANINE TAILS: A NOVEL TYPE OF PROTEIN MODIFICATION IMPLICATED IN NEURODEGENERATION
    THE JACKSON LABORATORY · Principal Investigator
Education:
  • 1996
    Ph.D.
    University of California, San Diego
  • 1990
    Master's of Science
    University of Sao Paulo
Courtney Miller

Courtney Miller Ph.D.

Director Of Academic Affairs And Professor
Phone: (561) 228-2958
Mailing Address:
130 SCRIPPS WAY BLDG 3B3
JUPITER FL 33458
Research Summary:

The Miller Lab operates as two parallel, but integrated branches. The first takes an in vivo approach to the neurobiology of memory, connecting behavior, circuits and molecular and cellular mechanisms to identify potential therapeutic targets in neuropsychiatric disorders with a memory component, such as substance use disorders and PTSD. The complementary side of my lab is focused on assay development, drug discovery and development, seeded by our basic research efforts, with a focus on molecular nanomotors. The latter has also led us to apply our therapeutics to cancers, such as glioblastoma and pancreatic cancer, to simultaneously prevent tumor cell proliferation and invasion/metastasis.

Publications:
Grants:
  • Apr 2024 ACTIVE
    Preclinical development of a precision therapy for a monogenic mental health disorder
    NATL INST OF HLTH · Principal Investigator
  • Jul 2023 ACTIVE
    The Impact of Individual Vulnerability to Stress on Alcohol and Drug Seeking
    NATL INST OF HLTH NINDS · Other
  • Apr 2023 ACTIVE
    Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for Glioblastoma
    NATL INST OF HLTH NINDS · Principal Investigator
  • Jan 2023 ACTIVE
    Intersection of causal neurodevelopmental disorder risk genes, cortical circuit function, and cognitive processing required for behavioral adaptions
    NATL INST OF HLTH NIMH · Co-Investigator
  • Sep 2022 ACTIVE
    Neurodevelopmental Disorder Risk Gene Regulation of Intrinsic Membrane Excitability: A Rheostat that Tunes Dendritic Morphogenesis to Regulate Circuit Assembly During Development
    NATL INST OF HLTH NIMH · Principal Investigator
  • Apr 2022 – Dec 2022
    Circuit-level substrates of ASD-related cognitive and behavioral impairments
    NATL INST OF HLTH NIMH · Principal Investigator
  • Apr 2022 – Feb 2024
    Integrated Platform for Discovery and Validation of Probes that Restore Protein Expression in Single-Gene Causes of Autism and Related Disorders
    NATL INST OF HLTH NIMH · Principal Investigator
  • Apr 2022 – Mar 2023
    Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for Glioblastoma
    NATL INST OF HLTH NINDS · Principal Investigator
  • Apr 2022 – Jun 2023
    Assessing the role of circRNAs in memory consolidation
    NATL INST OF HLTH NIMH · Co-Investigator
  • Apr 2022 ACTIVE
    Preventing alcohol seeking with a nonmuscle myosin II inhibitor under clinical development
    NATL INST OF HLTH NIAAA · Principal Investigator
  • Apr 2022 ACTIVE
    Myosin II regulation of actin dynamics and the selective vulnerability of methamphetamine- and opioid-associated memory
    NATL INST OF HLTH NIDA · Principal Investigator
  • Apr 2022 ACTIVE
    Targeting Go and Grow in Glioblastoma
    MAYO CLINIC · Principal Investigator
  • Apr 2022 ACTIVE
    Developing nonmuscle myosin II inhibitors for the treatment of glioblastoma
    NATL INST OF HLTH NINDS · Principal Investigator
  • Apr 2022 – Sep 2023
    Development of AI-driven model for anti-SUD drug development based on neuronal plasticity
    VERISIM LIFE · Principal Investigator
Education:
  • 2007-2009
    Technology Ventures Certification
    Collat School of Business
  • 2005
    Ph.D. in Neurobiology
    University of California, Irvine
  • 1999
    Bachelor's of Science in Biopsychology
    University of California, Santa Barbara
Louis Scampavia

Louis Scampavia Ph.D.

Senior Scientific Director: Department Of Molecular Medicine
Phone: (561) 228-2101
Mailing Address:
130 SCRIPPS WAY
JUPITER FL 33458
Physical Address:
Location A111
130 SCRIPPS WAY BLDG 1A1
JUPITER FL 33458
Research Summary:

Progress in drug discovery is often coupled to parallel advancements in instrument technology. In our department, High Throughput Screening (HTS) robotics is employed to accelerate the drug discovery process thorough full automation of large scale screening experiments. HTS technology can be used to execute and analyze hundreds of thousand of experiments against large compound libraries to identify a few select compounds of therapeutic value. These “therapeutic leads” provide important insight and basis for the medicinal development of novel drugs for clinical application.

Research efforts are currently focused on:

— Working with collaborators to develop biological assays for HTS compatibility.

— Performing exploratory HTS campaigns for drug lead discovery.

— Technology development and instrumentation for the advancement of HTS robotics.

Collaborative efforts are coordinated with a large community of scientists and include TSRI and UF faculty, Florida researchers, and academia often funded through the National Institutes of Health, Department of Defense and private foundations.

Publications:
Grants:
  • Jan 2024 ACTIVE
    An Innovative Approach to Identify Correctors of Metabolic Complications in HIV
    SCRIPPS RESEARCH INST · Co-Investigator
  • Oct 2023 ACTIVE
    Altos HTS Discovery for ISR Inhibitors 640K HTS with 1 counterscreen
    ALTOS LABS · Co-Investigator
  • Oct 2023 – Apr 2024
    TCAL USP11 Biochemcial FRET INH Assay 640K HTS Proprosal with 2 Counterscreens
    TAKEDA PHARM NORTH AMERICA · Co-Investigator
  • Jul 2023 ACTIVE
    Arvinas: Ataxin-2 Degraders HiBit cell based 665K HTS with 2 counterscreens
    ARVINAS OPERATIONS · Co-Investigator
  • May 2023 – Oct 2023
    Lilly NPY2R AG TR-FRET cAMP High Throughput Screen Assay 880K HTS Proposal with 1 Counterscreen
    SCIENCE EXCHANGE · Co-Investigator
  • May 2023 – Oct 2023
    TCAL TREM-2
    TAKEDA PHARM NORTH AMERICA · Co-Investigator
  • Apr 2023 ACTIVE
    Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for Glioblastoma
    NATL INST OF HLTH NINDS · Principal Investigator
  • Jan 2023 – Jan 2024
    Annexon Bio -Complement C1s Protease Fluorescence INH HTS Campaign with UF Scripps 640K Deck plus 1 Counterscreen
    ANNEXON · Co-Investigator
  • Dec 2022 – Nov 2023
    Kainomyx -PfMyo-A Absorbance INH HTS Campaign with UF Scripps 640K Deck plus 1 Counterscreen
    KAINOMYX · Co-Investigator
  • Oct 2022 – Dec 2023
    TCAL OMA-1 FRET Biochemical INH Assay 666K SDDL HTS Proposal with 1 Counterscreen
    TAKEDA PHARM NORTH AMERICA · Co-Investigator
  • Sep 2022 – Mar 2023
    Lilly AMY3R PAM TR-FRET cAMP High Throughput Screen Assay 665K HTS Proprosal with 1 Counterscreen
    SCIENCE EXCHANGE · Co-Investigator
  • Jul 2022 – Dec 2022
    TCAL OXR1 AG and PAM Ca++ High Throughput Screen Assay 665K HTS Proprosal with 2 Counterscreens
    TAKEDA PHARM NORTH AMERICA · Co-Investigator
  • Jun 2022 – Jan 2023
    HEK AAV2 Induction and GFP Reporter Assay 600K HTS
    THERMOFISHER SCIENTIFIC · Co-Investigator
  • Jun 2022 – Dec 2023
    Takeda TCAL GPCR HTS
    TAKEDA PHARM NORTH AMERICA · Co-Investigator
  • May 2022 ACTIVE
    Midwest AViDD Center – Project 3
    UNIV OF MINNESOTA · Principal Investigator
  • May 2022 ACTIVE
    Midwest AViDD Center – CORE B
    UNIV OF MINNESOTA · Principal Investigator
  • Apr 2022 – Feb 2024
    Integrated Platform for Discovery and Validation of Probes that Restore Protein Expression in Single-Gene Causes of Autism and Related Disorders
    NATL INST OF HLTH NIMH · Principal Investigator
  • Apr 2022 ACTIVE
    Identification of novel anthelmintics through a target-based screen of a parasite ion channel
    MEDICAL COLLEGE OF WISCONSIN · Principal Investigator
  • Apr 2022 ACTIVE
    Identification of small molecules for neurological complications of HIV and substance abuse comorbidity
    SCRIPPS RESEARCH INST · Co-Investigator
  • Apr 2022 ACTIVE
    Identification of REV-ERB inverse agonists for cancer immunotherapy
    NATL INST OF HLTH NCI · Principal Investigator
  • Apr 2022 – Aug 2023
    An Innovative Approach to Identify Correctors of Metabolic Complications in HIV
    SCRIPPS RESEARCH INST · Co-Investigator
  • Apr 2022 – Jun 2023
    High-Throughput Screen for the Oncoprotein MYC
    SCRIPPS RESEARCH INST · Co-Investigator
  • Apr 2022 – Mar 2023
    Drug Discovery for First-In-Class Myosin 10 Inhibitors as a Novel Target for Glioblastoma
    NATL INST OF HLTH NINDS · Principal Investigator
  • Apr 2022 – Sep 2022
    Parallel Multimodal High-throughput screening to identify activators of the orexin receptors
    NATL INST OF HLTH NIMH · Principal Investigator
  • Apr 2022 – Sep 2022
    Tandem Multi-modal Plate Readers for a High Throughput Screening platform
    NATL INST OF HLTH OD · Principal Investigator
  • Apr 2022 – May 2022
    Identification of Chemical Probes for the Orphan Nuclear Receptor NR2F6
    NATL INST OF HLTH NCI · Principal Investigator
  • Apr 2022 – Apr 2022
    Development of neutral ceramidase inhibitor tool compounds
    THE RES FOU FOR THE SUNY STONY BROOK UNI · Principal Investigator
Education:
  • 1996
    Doctor of Philosophy in Chemistry
    University of Washington, Seattle
  • 1991
    Bachelor's of Science in Chemistry
    University of Washington, Seattle
  • 1979
    Bachelor's of Science in Genetics
    University of California, Berkeley
Timothy P Spicer

Timothy P Spicer Ph.D.

Senior Scientific Director, Department Of Molecular Medicine
Phone: (561) 228-2150
Mailing Address:
130 Scripps Way #1A1
The Herbert Wertheim UF Scripps Institute
Jupiter FL 33458
Research Summary:

The focus of our research involves enabling technologies for High Throughput Screening (HTS) of any target of unmet therapeutic need. Our facility supports scientist and faculty locally as well as those in the US and throughout the world. We do this by implementing their biological applications into high density plates for HTS. The breadth of biology we deal with is virtually unlimited due to the diversity of skill sets of the scientist and engineers within our group as well as the expanded capability of the readers associated to our system. We operate a fully automated 1536 well compatible platform and perform HTS on large compound libraries such as the Scripps Drug Discovery Library (645K) or small focused collections (FDA approved drugs). We have expertise in microfluidics, low nanoliter volume liquid handling, ultra-sensitive plate reader technologies and informatics set-up to handle large volume data sets. Key components are high-content readers, imaging detectors such as the ViewLux and FLIPR Tetra, as well as pintool and acoustic transfer devices. Through collaborative efforts we have successfully translated multiple small molecules into the clinics. We are open to any pharmacology desired (agonist, PAMs, NAMs, inverse agonist, etc.) vs. kinases, GPCR, NHRs, proteases, phenotypic assays, etc. which can be applied to any therapeutic area; i.e. CNS, infectious diseases, cardiovascular, oncology, metabolic diseases. In addition, we are currently funded (R33CA206949) to develop 3D spheroid based uHTS assays for the purpose of testing molecules in a more phenotypically relevant format to cancer biology.

Publications:
Education:
  • 2019
    Ph.D. in Medicine
    University of Queensland
  • 1996
    Master's of Microbiology
    State University of New York Health Science Center
  • 1990
    Bachelor's of Science in Biology
    State University of New York at Albany
Donna Zhang

Donna Zhang

Dr. Herbert A. Wertheim Professor
Phone: (561) 228-2560
Physical Address:
130 SCRIPPS WAY # B258F
JUPITER FL 33458

Dr. Donna D. Zhang, Ph.D., is a distinguished molecular toxicologist renowned for her groundbreaking research in understanding the mechanisms underlying various diseases and developing innovative therapeutic strategies. She earned her Ph.D. in Molecular Toxicology from New York University’s Nelson Institute of Environmental Medicine in 1997, focusing on the identification and characterization of the novel gene Cap43 induced by Ni2+ compounds. Throughout her illustrious career, she has held several esteemed academic positions, including her current role as the Dr. Herbert A. Wertheim Professor at the Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology at the University of Florida. Prior to this, Dr. Zhang served as the Musil Family Endowed Chair in Drug Discovery at the College of Pharmacy at the University of Arizona, where she made significant contributions to the field through her research and teaching.

With a passion for education and mentorship, Dr. Zhang has made significant contributions to the field through her teaching and supervision of Ph.D. students. She has developed and coordinated various courses in pharmacology and toxicology, shaping the next generation of scientists and pharmacists. Additionally, she actively engages in service and outreach activities both within her institution and externally, serving on numerous committees and review panels for prestigious organizations such as NIH and the Society of Toxicology. Dr. Zhang’s dedication to advancing scientific knowledge and her commitment to training future leaders in the field underscore her invaluable contributions to the scientific community.

Research Summary:

My research endeavors explore the intricate mechanisms of NRF2 redox biology, the pathogenesis of arsenic, and the development of preclinical drugs targeting NRF2. The goal is to leverage the body’s own defense systems, particularly the NRF2 pathway, to combat human diseases. NRF2, a pivotal transcription factor, orchestrates the cellular defense against environmental insults by regulating genes critical for maintaining redox and metabolic homeostasis.

Since NRF2’s discovery, it has been championed for its protective role against oxidative stress. Nonetheless, research from my laboratory has exposed its paradoxical role in cancer progression and therapy resistance. Our recent pioneering work has linked NRF2 high expression in certain cancers to enhanced survival and resistance to a new class of cell death, ferroptosis. These studies have significant implications, as NRF2 inhibition could transform therapeutic approaches for treatment-resistant cancers.

Additionally, my team’s research has implicated persistent NRF2 activation in the carcinogenic and diabetogenic effects of arsenic, a notorious environmental toxin affecting millions globally. This has set the stage for the development of specific NRF2 inhibitors, a yet unmet need in the field, to dissect NRF2’s detrimental roles in disease.

In summary, my lab’s efforts are directed towards: Unraveling the NRF2 signaling network. Deciphering NRF2 dysregulation in arsenic-induced carcinogenesis and diabetes. Developing NRF2-centric therapeutic strategies, including small molecules and nanobodies. Investigating the molecular biology of the CNC family proteins (NRF1, NRF2, and NRF3). The ultimate aim is to mitigate the impact of diseases exacerbated by environmental factors like arsenic, through innovative NRF2-targeted interventions.

Research Interests:
  • Cancer
  • Diabetes
  • Ferroptosis
  • NRF2
  • NRF2-Keap-ARE pathway
  • arsenic toxicity
  • autophagy
  • redox biology
Publications:
Education:
  • 1997
    Ph.D. in Molecular Toxicology
    New York University, Nelson Institute of Environmental Medicine, New York, New York.
  • 1993
    M.S. in Molecular Toxicology
    New York University, Nelson Institute of Environmental Medicine, New York, New York.
Jason Yuan

Jason Yuan

Professor Of Molecular Medicine
Phone: (561) 228-2624
Physical Address:
B #258G
130 SCRIPPS WAY
JUPITER FL 33458

Jason Yuan, M.D., Ph.D., is a distinguished Professor at the Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology and serves as the Assistant Vice President for Research at UF Health, the University of Florida-Scripps Research in Florida.

He embarked on his academic journey by earning his medical degree from Suzhou Medical College (Suzhou, China) in 1983. Subsequently, he obtained his doctoral degree in physiology from Peking Union Medical College (Beijing, China) in 1993. Dr. Yuan further enriched his expertise through postdoctoral training in the University of Maryland at Baltimore. Dr. Yuan’s early research focused on unraveling the intricate cellular and molecular mechanisms underlying hypoxic pulmonary vasoconstriction. His groundbreaking work encompassed the electrophysiology of ion channels and transporters in vascular smooth muscle and endothelial cells, as well as the regulation of excitation-contraction (EC) coupling across various cell types, including smooth muscle cells, neurons, and cardiomyocytes. His seminal contributions have significantly advanced our understanding of pulmonary vascular physiology and pathophysiology. Dr. Yuan’s current research is primarily focused on defining pathogenic mechanisms of pulmonary arterial hypertension (PAH) and developing novel therapeutic approaches for PAH and other subtypes of pulmonary hypertension.

Notably, Dr. Yuan’s research in pulmonary vascular disease has propelled the field forward, shedding light on the pathogenic roles of ion channels and membrane receptors. His pioneering insights have paved the way for innovative therapeutic approaches to combat these diseases. Since 1993, Dr. Yuan has been continuously funded by the National Institutes of Health (NIH), a testament to the significance and impact of his research endeavors.

In recognition of his exemplary contributions to science, Dr. Yuan has been honored as a Fellow of prestigious organizations such as the American Association for the Advancement of Science, the American Heart Association, the American Thoracic Society, and The American Physiological Society. Additionally, he has been recognized as a Guggenheim Fellow and is an elected Member of the American Society for Clinical Investigation and the Association of American Physicians.

Dr. Yuan’s leadership extends beyond his research pursuits, as evidenced by his active involvement in advisory committees and editorial boards. He has chaired influential bodies such as the Respiratory Integrative Biology and Translational Research study section of the NIH and the Pulmonary Circulation Assembly of the American Thoracic Society. Currently, he serves as the Editor-in-Chief of the journal Pulmonary Circulation and on the editorial board of the American Journal of Physiology Cell Physiology, Circulation Research, American Journal of Respiratory and Critical Care Medicine.

Furthermore, Dr. Yuan’s scholarly contributions are evident in his role as a leading editor of several seminal books in the field of pulmonary circulation. His comprehensive reference book, “Textbook of Pulmonary Vascular Disease,” stands as a cornerstone resource for researchers and clinicians alike. Additionally, he has edited or co-edited numerous other influential works, further cementing his status as a leading authority in his field.

In collaboration with esteemed colleagues, Dr. Yuan has co-authored “Ganong’s Review of Medical Physiology,” a widely acclaimed resource in medical education.

Through his relentless pursuit of scientific excellence and commitment to advancing our understanding of pulmonary vascular diseases, Dr. Jason Yuan has made indelible contributions to the field of biomedical research and continues to inspire future generations of scientists.

Research Summary:

Dr. Jason Yuan’s illustrious academic career has been marked by groundbreaking research and significant contributions to the field of pulmonary vascular disease. Beginning as a Research Assistant Professor of Medicine at the University of Maryland School of Medicine from 1993 to 1998, he established himself as a pioneer in translational research by initiating projects using lung tissues and cells from patients with idiopathic pulmonary arterial hypertension (IPAH). His work focused on unraveling the pathogenic mechanisms underlying this disease.

In recognition of his outstanding contributions, Dr. Yuan was awarded the prestigious Parker B. Francis Fellowship from the Francis Families Foundation in 1994 and the Giles F. Filley Memorial Award for Excellence in Respiratory Physiology and Medicine from the American Physiological Society in 1995. Additionally, he was honored as the recipient of the Cournand and Comroe Young Investigator Award by the American Heart Association in 1995, further solidifying his reputation as a promising young investigator in the field.

Dr. Yuan’s dedication to advancing therapeutic approaches for pulmonary vascular disease led to his receipt of an Established Investigator Award from the American Heart Association in 1998. His pioneering work in identifying novel therapeutic strategies earned him recognition as one of the leading researchers in the field of pulmonary vascular disease and right heart failure.

In 1999, Dr. Yuan joined the University of California, San Diego, where he continued to expand his research interests to include chronic thromboembolic pulmonary hypertension, the functional role of ion channels in stem cell biology, and pharmacogenetics associated with pulmonary arterial hypertension. During his tenure at UC San Diego, he held key leadership positions, serving as Vice Chair for Research in the Department of Medicine from 2007 to 2010 and Associate Director for Research Training in the Division of Pulmonary and Critical Care Medicine from 2003 to 2010.

Dr. Yuan’s commitment to advancing translational medicine led him to the University of Illinois at Chicago in July 2010, where he assumed the role of Program Director in the newly established Institute for Personalized Respiratory Medicine. Additionally, he served as Vice Chair for Scholarly Activities in the Department of Medicine and Director of the Program in Pulmonary Vascular Disease and Right Heart Dysfunction at the Center for Cardiovascular Research.

In May 2010, Dr. Yuan was appointed Associate Vice President for Translational Health Sciences at the University of Arizona, where he also became the founding Chief of the Division of Translational and Regenerative Medicine in the Department of Medicine. His leadership and expertise have significantly advanced the field of translational medicine, paving the way for innovative approaches to personalized healthcare.

Throughout his career, Dr. Yuan’s unwavering dedication to scientific inquiry and his pioneering research have earned him numerous accolades and recognition as a leading authority in pulmonary vascular disease and translational medicine. His groundbreaking work continues to impact the lives of patients and inspire future generations of researchers in the field.

Research Interests:
  • acute pulmonary hypertension resulting from pulmonary embolism
Publications: