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
  • In June 2012, 28-year-old Emily Bennett Taylor was getting ready to celebrate her second wedding anniversary with her college sweetheart when she discovered that she had Stage 4 lung cancer. Taylor was a former college athlete, had led a healthy and active lifestyle and had never smoked. She quickly began treat...
  • “Skin cancer” was pretty much the last thing on the mind of a healthy, outdoorsy kid like Tanner Harbin. “I like hockey – playing it and watching it,” the 23-year-old from San Dimas said. “I like to go off-roading with my dad – we have a Jeep and we have a cabin up in Big Bear, so […]
  • Skin cancer is an enticing field to be in these days. Just ask Laleh Melstrom, M.D. M.S., one of City of Hope’s newest surgeons. “In the last few years, melanoma has been the type of cancer that has really shown the most progress in terms of treatments,” Melstrom said. “It’s the one cancer in 2015 that is...
  • Skin cancer is the most common type of cancer in the United States today, and its incidence is on the rise. Forty to 50 percent of light-skinned Americans who live to age 65 will have skin cancer at least once in their lives. Most of these skin cancers – about 3.5 million cases – are the […]
  • The connection between lifestyle and cancer is real. Knowing that, what can individuals do to lower their risk? City of Hope physicians recently came together to answer that precise question, explaining the links between cancer and the choices we make that affect our health. Moderator Vijay Trisal M.D., medical...
  • White button mushrooms seem fairly innocuous as fungi go. Unlike portabellas, they don’t center stage at the dinner table, and unlike truffles, they’re not the subject of gourmand fervor. But appearances can be deceiving when it comes to these mild-mannered Clark Kents of the food world. In a study ...
  • Doctors often recommend preventive screenings for several cancers, based on hereditary or genetic factors, but brain tumors aren’t one of them. Primary brain tumors, which originate in the brain rather than spreading from another location, seem to develop at random, and doctors have little insight into wh...
  • Stopping cancer starts with research. To that end, STOP CANCER has awarded $525,000 in grants to City of Hope for 2015, supporting innovative research projects and recognizing the institution’s leadership in advancing cancer treatment and prevention. Founded in 1988, STOP CANCER underwrites the work of le...
  • Cancer may not be the disease many people think it is. Normally, cancer is considered to be a disease in which cells multiply at an extremely high, and unusual, rate – increasing the likelihood of genetic mutations. But increasingly, leading researchers at City of Hope and elsewhere are contending that cancer i...
  • “Of all forms of inequality, injustice in the health care system is the most shocking and inhumane.” By the time the Rev. Martin Luther King Jr. spoke those words in Chicago in 1966, the Civil Rights Act had been passed, the Voting Rights Act was the law of the land and the March on Washington was […]
  • Eight years ago, Matthew Loscalzo surprised himself by accepting the offer to become City of Hope’s administrative director of the Sheri & Les Biller Patient and Family Resource Center and executive director of the Department of Supportive Care Medicine. At the time, he was administrative director of the Sc...
  • The mental fog that patients can experience after undergoing chemotherapy treatment for cancer has a name: “chemo brain.” “Many patients report hearing or reading about chemotherapy-related cognitive deficits, but few are actually prepared to deal with these changes,” said Celina Lemon, M.A., an occupational th...
  • Cancer treatments have improved over the years, but one potential source of treatments and cures remains largely untapped: nature. Blueberries, cinnamon, xinfeng, grape seed (and skin) extract, mushrooms, barberry and pomegranates all contain compounds with the potential to treat or prevent cancer. Scientists a...
  • In the U.S., there are more new cases of skin cancer than the combined incidence of cancers of the breast, prostate and lung, according to the American Cancer Society. Each year, 5 million people are treated for skin cancer. Here, Hans Schoellhammer, M.D., assistant clinical professor at City of Hope | Ant...
  • As public health experts know, health improvement starts in the community. Now, City of Hope  has been recognized for its efforts to improve the lives of residents of its own community. The institution will receive funding from the Institute for Healthcare Improvement  to support promising community-based work ...