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Molecular Pharmacology

Department of Molecular Pharmacology
Current therapeutic options for the majority of advanced cancers remain inadequate, highlighting the need for discovery of new anticancer agents directed against novel targets. The department's mission is to investigate the effectiveness of cancer chemotherapeutic agents in order to develop novel molecular-targeted cancer therapies. We study drug mechanisms in DNA damage and repair, signal transduction and DNA synthesis. In addition, we seek to understand mechanisms of drug resistance. Understanding these mechanisms allows us to design more effective drugs.

 

We continue to expand our clinical research in pharmacokinetic, pharmacodynamic and, more recently, pharmacogenomics studies of investigational drugs, which enable us to obtain a clear picture of how these drugs impact the patient. The department aims to bridge the gap between the development of promising new drugs and their application in the clinic.

 

Molecular Pharmacology
Precise regulation of cellular signaling is important for cell growth and proliferation, cell metabolism and apoptosis ; dysregulation of cell signaling can lead to the development of cancer. Cancer therapeutics targets theses alterations in intracellular and intercellular signaling. In our department, we study Cancer metabolism, Signal transduction and Epigenetics, and Tumorigenesis and progression.

 

Understanding how cancer advances by altering cell metabolism. Tumorigenesis is often associated with altered nucleotide metabolism, characterized by dysregulated Ribonucleotide Reductase (RR), and altered carbohydrate metabolism, characterized by increased glucose uptake and elevated lactic acid production under aerobic conditions. Notably, it was recently reported that RRM2B, the small subunit of RR, serves a crucial role in maintaining chromosomal stability and preventing chronic inflammation-associated tumorigenesis. We are also focused on understanding the autophagy regulatory mechanisms and biological functions in cancer. Autophagy is cell catabolic process in response to stress. Special emphases are focused on the involvement of ROS and oxidative stress from mitochondria to induce autophagy.

 

Understanding how cancer cells survive against therapeutics by altering cell signaling. Original DNA damage & Repair, add Ub and SUMO.

 

Understanding how cancer progresses by promoting cell survival. We are investigating how changes in androgen receptor (AR) signaling cause prostate tumorigenesis as well as progression from androgen-sensitive to castration-resistant prostate cancer. In conjunction, we are developing drugs that inhibit AR signaling by novel mechanisms.

Clinical Pharmacology
Once target molecules are identified and promising drug candidates are selected, it is crucial to understand the clinical pharmacology of the compounds, that is, how they behave in actual patients. Key research areas within Clinical Pharmacology include pharmacokinetics (the study of drug disposition), pharmacodynamics (drug effects) and pharmacogenomics - the study of genetically inherited determinants of drug response and toxicity.

Translational Research
Molecular pharmacology department uses sophisticated techniques such as computer modeling to identify novel therapeutic targets, e.g., receptors, in cancer. This enables our researchers to design new compounds as well as screen leading drug candidates, such as natural products, from our drug screening program that fit the mechanism of action dictated by the specified molecular target. This process is called target validation.

Translational research involves conducting pre-clinical studies on experimental drug therapies and post-clinical analyses on clinical samples.Laboratory-based investigationsexamine at the molecular level the mechanisms of action and resistance of anticancer agents, including both novel and traditional chemotherapeutic drugs, immunotherapeutics and combinations of anticancer agents and antibodies. The lab helps to facilitate communication between scientists and clinicians studying molecular genetic responses of cells to potential therapeutic compounds, as well as to identify and/or develop biomarker s for targeted therapy.
 

Laboratory Research

Yun Yen, M.D., Ph.D.
The laboratory of Yun Yen, M.D., Ph.D., is involved in: (1) elucidating the molecular mechanism of chemotherapeutic drug resistance by studying the enzyme ribonucleotide reductase (RR); (2) developing novel chemotherapeutic agentsuseful forcircumventing drug resistance in cancer by inhibiting RR; (3) developing surrogate markers for enhancing cancer drug therapeutic effect from human samples collected from RR inhibitor studies; and (4) studying the role of the growth arrest DNA damage-inducible gene 45β (GADD45 β) in human hepatocellular cancer and FGFR3 in myeloma.

 

David K. Ann, Ph.D.
The research program goals of David K. Ann, Ph.D., are to understand both the molecular mechanisms and signal transduction processes that maintain genomic integrity following DNA damage and to develop novel molecular therapies for human cancers by targeting dysfunctional or deregulated responses to DNA damage. The DNA damage-induced signaling pathway involves a kinase-dependent signaling cascade that regulates cell cycle progression, DNA repair and apoptosis (cell death). It is the coordination of these events that ensures genomic stability. His current interest is to decipher the signaling transduction pathways and molecular mechanisms underlying genomic instability and to enhance the tumor selectivity or DNA-targeted agents. Specifically, he currently works on (1) HMGA2 and genomic instability, (2) SUMOylation and DNA damage response and (3) autophagy and drug resistance.

Warren Chow, M.D.
Dr. Chow’s group focuses on the development of novel therapeutics for treatment of sarcomas, which are rare cancers of connective tissues. He has focused on new therapies for (1) Ewing's sarcoma/primitive neuroectodermal tumors by targeting surface membrane tyrosine kinase receptors with small molecule inhibitors; (2) chondrosarcomas with a novel multitargeted antifolate drug due to the finding of frequent deletions of the methylthioadenosine phosphorylase gene; and (3) liposarcomas by upregulating genes integral for two distinct mechanisms of programmed cell death, apoptosis and autophagy.

Edward Newman, Ph.D.– Molecular Pharmacology
Dr. Newman’s research concentrates on developing novel DNA methyltransferase inhibitors for cancer therapy.

Jeremy Jones, Ph.D.
Jeremy Jones, Ph.D., is an Assistant Professor in the Department of Molecular Pharmacology. His lab studies the androgen receptor and its involvement in human diseases such as prostate cancer.

Timothy W. Synold, Pharm.D.
The laboratory of Timothy W. Synold, Pharm.D., is involved in: (1) the molecular and clinical pharmacology of drugs targeting mitotic cell division; (2) inducible drug clearance and tumor cell resistance through the orphan nuclear receptor, SXR; (3) regulation of MDR1 expression in vivo and in vitro; (4) pharmacokinetics and pharmacodynamics of anticancer agents in phase I and II settings; and (5) the clinical pharmacology of anticancer agents in special patient populations (e.g., elderly patients and patients with hepatic or renal insufficiency).
 
Overview
Beckman Research Institute of City of Hope is responsible for fundamentally expanding the world’s understanding of how biology affects diseases such as cancer, HIV/AIDS and diabetes.
 
 
Research Departments/Divisions

City of Hope is a leader in translational research - integrating basic science, clinical research and patient care.
 

Research Shared Services

City of Hope embodies the spirit of scientific collaboration by sharing services and core facilities with colleagues here and around the world.
 

Our Scientists

Our research laboratories are led by the best and brightest minds in scientific research.
 

City of Hope’s Irell & Manella Graduate School of Biological Sciences equips students with the skills and strategies to transform the future of modern medicine.
Develop new therapies, diagnostics and preventions in the fight against cancer and other life-threatening diseases.
 
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