A National Cancer Institute-designated Comprehensive Cancer Center

Make an appointment: 800-826-HOPE
Molecular Pharmacology Bookmark and Share

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).
 

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

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.
 


NEWS & UPDATES
  • “World-class expertise,” “leading-edge research” and “compassionate patient care” are not just words at City of Hope; they’re a way of life. No one knows this more than City of Hope’s patients. On New Year’s Day, six of those patients and their loved ones – ...
  • The protein HER2 is most commonly associated with breast cancer, but it also plays a role in several other cancers — including  esophageal cancer. Using this knowledge and the drug trastuzumab (Herceptin), which targets HER2, City of Hope researchers are conducting clinical trials with the hope of improving sur...
  • A new therapy is offering hope to patients with a certain form of acute lymphoblastic leukemia (ALL). The drug recently received approval by the U.S. Food and Drug Administration, thanks in part to studies conducted by Anthony Stein, M.D., at City of Hope. The drug Blincyto, also known by its generic name of bl...
  • Too often, the symptoms of esophageal cancer are mistaken for those of more benign conditions. That’s an easy mistake to make because many people do experience such symptoms every now and then, including trouble swallowing, hoarseness, coughing, frequent vomiting or hiccupping, even the more alarming ches...
  • Cancer cells are voracious eaters. Like a swarm of locusts, they devour every edible tidbit they can find. But unlike locusts, when the food is gone, cancer cells can’t just move on to the next horn o’ plenty. They have to survive until more food shows up — and they do. Mei Kong, Ph.D., assistant […]
  • On Jan. 1, 2015, six City of Hope patients who have journeyed through cancer will welcome the new year with their loved ones atop City of Hope’s Tournament of Roses Parade float. The theme of the float is “Made Possible by HOPE.” The theme of the parade is “Inspiring Stories.” Repr...
  • When 25-year-old Angelina Mattos was diagnosed with Stage 4 oral cancer earlier this year, she learned that her only hope of survival was through the removal of her tongue, a surgery that leaves people without the ability to talk or eat normally, sometimes permanently ending their ability to speak. After hearin...
  • Two years ago, Joselyn Miller and her family sat together as stem cells from her brother’s bone marrow were infused into her – a precious gift of life that the family is excited to have the chance to pass to another patient in need. Today, the stem cell recipient is healthy. Her 23-year-old son Rex, who […...
  • Even as the overall rate of oral cancers in the United States steadily declines, the rate of tongue cancer is increasing — especially among white females ages 18 to 44. An oral cancer diagnosis, although rare, is serious. Only half of the people diagnosed with oral cancer are still alive after five years, accor...
  • Sometimes cancer found in the lungs is not lung cancer at all. It can be another type of cancer that originated elsewhere in the body and spread, or metastasized, to the lungs through the bloodstream or lymphatic system. These tumors are called lung metastases, or metastatic cancer to the lungs, and are not the...
  • When it comes to research into the treatment of hematologic cancers, City of Hope scientists stand out. One study that  they presented this week at the annual meeting of the American Society of Hematology suggests a new standard of care for HIV-associated lymphoma, another offers promise for the treatment of re...
  • Patients with HIV-associated lymphoma may soon have increased access to the current standard of care for some non-HIV infected patients – autologous stem cell transplants. Impressive new data, presented Monday at the annual meeting of the American Society of Hematology (ASH) in San Francisco, indicate that HIV-...
  • On Jan. 1, 2015, six City of Hope patients who have journeyed through cancer will welcome the new year with their loved ones atop City of Hope’s Tournament of Roses Parade float. The theme of the float is “Made Possible by HOPE.” The theme of the Rose Parade is “Inspiring Stories.”...
  • The holidays can create an overwhelming urge to give to people in need — especially to sick children and families spending the holidays in a hospital room. That’s a good thing. Holiday donations of toys and gifts can bolster the spirits, and improve the lives, of people affected by illness, and hospitals ...
  • On Jan. 1, 2015, six City of Hope patients who have journeyed through cancer will welcome the new year with their loved ones atop City of Hope’s Tournament of Roses Parade float. The theme of the float is “Made Possible by HOPE.” The theme of the parade is “Inspiring Stories.” Here...