A National Cancer Institute-designated Comprehensive Cancer Center

Make an appointment: 800-826-HOPE
Kong, Mei, Ph.D. Bookmark and Share

Laboratory of Mei Kong, Ph.D.

Signal transduction and Cancer Metabolism
Tumor cells often display fundamental changes in metabolism and increase their uptake of nutrients to meet the increased bioenergetic demands of proliferation.  Glucose and glutamine are two main nutrients whose uptake is directly controlled by signal transduction and are essential for tumor cell survival and proliferation.  Altered glucose metabolism in cancer cells is termed the Warburg effect, which describes the propensity of most cancer cells to take up glucose avidly and convert it primarily to lactate, despite available oxygen.   In addition to glucose, glutamine is another essential nutrient whose uptake is directly controlled by oncogenes, and it is critical for cancer cell survival and proliferation.  During tumor growth, increased uptake of nutrients and rapid accumulation of cells can outstrip the supply of essential nutrients, including glucose and glutamine.  How tumor cells survive these temporary periods of nutrient deprivation is unclear, but is necessary for tumorigenesis to persist.  The major goal of our laboratory is to delineate the strategies used by tumor cells to survive periods of nutrient deprivation and then to develop novel therapies targeting nutrient-sensing pathways of neoplastic cells.  Exciting progress has been made over the past 20 years in elucidating how cancer cells survive glucose deprivation via mTOR, AMPK and p53 pathway.  In contrast, less is known about the signal transduction pathways that regulate tumor cells’ survival during glutamine deprivation, in spite of the evidence that has been noticed for many years, that glutamine fell from a high level in normal tissue to a level not detectable in different solid tumors.  Thus, identifying the critical regulators that control tumor cell survival during glutamine deprivation may lead to the development of novel and safer cancer therapies.  We recently discovered that protein phosphatase 2A (PP2A)-associated protein, α4, plays a conserved role in glutamine sensing. α4 promotes assembly of an adaptive PP2A complex containing the B55α regulatory subunit via providing the catalytic subunit upon glutamine deprivation. Moreover, B55α is specifically induced upon glutamine deprivation in a ROS-dependent manner to activate p53 and promote cell survival. B55α activates p53 through direct interaction and dephosphorylation of EDD, a negative regulator of p53. Importantly, the B55α-EDD-p53 pathway is essential for cancer cell survival and tumor growth under low glutamine conditions in vitro and in vivo. In future work, we will focus on understanding how p53 activation regulates tumor cell survival under glutamine deprivation, and identify critical p53 targets that contribute to cancer cell survival under glutamine limitation.  Our long-term goal is to identify the signals that allow communication between oncogenic pathways and tumor cell metabolism and develop novel therapeutics targeting metabolic differences between rapidly-proliferating cancer cells and normal cells.
 
Regulation of Protein Phosphatase 2A Complexes
Reversible protein phosphorylation is the major regulatory mechanism used by cells to respond to environmental and nutritional stresses.  Aberrant regulation of this activity leads to dysregulated cellular behavior and disease phenotypes, including many forms of cancer. Although we know much about how protein kinases function in specific signaling governed by phosphorylation, whether protein phosphatases are also regulated and actively function in the process to counteract kinase function has not been established. Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase that regulates many signaling pathways. Unlike kinases, serine/threonine phosphatases are promiscuously active and their specificity is governed largely by associated proteins. Thus, the specificity of PP2A is conferred by assembly of a trimeric complex including a catalytic C subunit, a scaffolding A subunit, and one of the sixteen regulatory B subunits. In addition to interacting with conventional A and B subunits, the C subunit reportedly forms two other distinct complexes with proteins designated α4 (Tap42 in yeast) and Tiprl (Tip41 in yeast).  Our laboratory also interested in characterizing molecular mechanisms underlying the response of PP2A complexes to stress signals.
 
For more information on Dr. Kong, please click here.

Mei Kong, Ph.D. Lab Members

Lab Members
 
Jenny Davies, Ph.D
Postdoctoral Fellow
626-256-4673, ext.30158
jedavies@coh.org
 
Min Pan, Ph.D.
Postdoctoral Fellow
626-256-4673 ext.  30158
minoan@coh.org

Michael Reid, B.S.
Graduate Student
626-256-4673, ext. 30158
mrieda@coh.org
 
Kimberly Rosales, Ph.D.
Postdoctoral Fellow
626-256-4673, ext. 30158
krosales@coh.org
 
Xazmin Lowman, Ph.D
Postdoctoral Fellow
626-256-4673, ext. 64450
 

Kong, Mei, Ph.D.

Laboratory of Mei Kong, Ph.D.

Signal transduction and Cancer Metabolism
Tumor cells often display fundamental changes in metabolism and increase their uptake of nutrients to meet the increased bioenergetic demands of proliferation.  Glucose and glutamine are two main nutrients whose uptake is directly controlled by signal transduction and are essential for tumor cell survival and proliferation.  Altered glucose metabolism in cancer cells is termed the Warburg effect, which describes the propensity of most cancer cells to take up glucose avidly and convert it primarily to lactate, despite available oxygen.   In addition to glucose, glutamine is another essential nutrient whose uptake is directly controlled by oncogenes, and it is critical for cancer cell survival and proliferation.  During tumor growth, increased uptake of nutrients and rapid accumulation of cells can outstrip the supply of essential nutrients, including glucose and glutamine.  How tumor cells survive these temporary periods of nutrient deprivation is unclear, but is necessary for tumorigenesis to persist.  The major goal of our laboratory is to delineate the strategies used by tumor cells to survive periods of nutrient deprivation and then to develop novel therapies targeting nutrient-sensing pathways of neoplastic cells.  Exciting progress has been made over the past 20 years in elucidating how cancer cells survive glucose deprivation via mTOR, AMPK and p53 pathway.  In contrast, less is known about the signal transduction pathways that regulate tumor cells’ survival during glutamine deprivation, in spite of the evidence that has been noticed for many years, that glutamine fell from a high level in normal tissue to a level not detectable in different solid tumors.  Thus, identifying the critical regulators that control tumor cell survival during glutamine deprivation may lead to the development of novel and safer cancer therapies.  We recently discovered that protein phosphatase 2A (PP2A)-associated protein, α4, plays a conserved role in glutamine sensing. α4 promotes assembly of an adaptive PP2A complex containing the B55α regulatory subunit via providing the catalytic subunit upon glutamine deprivation. Moreover, B55α is specifically induced upon glutamine deprivation in a ROS-dependent manner to activate p53 and promote cell survival. B55α activates p53 through direct interaction and dephosphorylation of EDD, a negative regulator of p53. Importantly, the B55α-EDD-p53 pathway is essential for cancer cell survival and tumor growth under low glutamine conditions in vitro and in vivo. In future work, we will focus on understanding how p53 activation regulates tumor cell survival under glutamine deprivation, and identify critical p53 targets that contribute to cancer cell survival under glutamine limitation.  Our long-term goal is to identify the signals that allow communication between oncogenic pathways and tumor cell metabolism and develop novel therapeutics targeting metabolic differences between rapidly-proliferating cancer cells and normal cells.
 
Regulation of Protein Phosphatase 2A Complexes
Reversible protein phosphorylation is the major regulatory mechanism used by cells to respond to environmental and nutritional stresses.  Aberrant regulation of this activity leads to dysregulated cellular behavior and disease phenotypes, including many forms of cancer. Although we know much about how protein kinases function in specific signaling governed by phosphorylation, whether protein phosphatases are also regulated and actively function in the process to counteract kinase function has not been established. Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase that regulates many signaling pathways. Unlike kinases, serine/threonine phosphatases are promiscuously active and their specificity is governed largely by associated proteins. Thus, the specificity of PP2A is conferred by assembly of a trimeric complex including a catalytic C subunit, a scaffolding A subunit, and one of the sixteen regulatory B subunits. In addition to interacting with conventional A and B subunits, the C subunit reportedly forms two other distinct complexes with proteins designated α4 (Tap42 in yeast) and Tiprl (Tip41 in yeast).  Our laboratory also interested in characterizing molecular mechanisms underlying the response of PP2A complexes to stress signals.
 
For more information on Dr. Kong, please click here.

Laboratory Members

Mei Kong, Ph.D. Lab Members

Lab Members
 
Jenny Davies, Ph.D
Postdoctoral Fellow
626-256-4673, ext.30158
jedavies@coh.org
 
Min Pan, Ph.D.
Postdoctoral Fellow
626-256-4673 ext.  30158
minoan@coh.org

Michael Reid, B.S.
Graduate Student
626-256-4673, ext. 30158
mrieda@coh.org
 
Kimberly Rosales, Ph.D.
Postdoctoral Fellow
626-256-4673, ext. 30158
krosales@coh.org
 
Xazmin Lowman, Ph.D
Postdoctoral Fellow
626-256-4673, ext. 64450
 
Our Scientists

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

Beckman Research Institute of City of Hope is internationally  recognized for its innovative biomedical research.
City of Hope is one of only 41 Comprehensive Cancer Centers in the country, the highest designation awarded by the National Cancer Institute to institutions that lead the way in cancer research, treatment, prevention and professional education.

Learn more about
City of Hope's institutional distinctions, breakthrough innovations and collaborations.
 
Develop new therapies, diagnostics and preventions in the fight against cancer and other life-threatening diseases.
 
Support Our Research
By giving to City of Hope, you support breakthrough discoveries in laboratory research that translate into lifesaving treatments for patients with cancer and other serious diseases.
 
 
 
 


NEWS & UPDATES
  • The outlook and length of survival has not changed much in the past 25 years for patients suffering from an aggressive form of pancreatic cancer known as pancreatic ductal adenocarcinoma (PDAC). These patients still have few options for therapy; currently available therapies are generally toxic and do not incre...
  • “With bladder cancer, the majority of patients that I see can be cured,” said urologist Kevin Chan, M.D., head of reconstructive urology at City of Hope. “The challenge is to get patients the same quality of life that they had before surgery.” To meet this challenge, Chan and the urologic team at City of Hope [...
  • Already pioneers in the use of immunotherapy, City of Hope researchers are now testing the bold approach to cancer treatment against one of medicine’s biggest challenges: brain cancer. This month, they will launch a clinical trial using patients’ own modified T cells to fight advanced brain tumors. One of but a...
  • Brain cancer may be one of the most-frightening diagnoses people can receive, striking at the very center of who we are as individuals. Further, it often develops over time, causing no symptoms until it’s already advanced. Listen to City of Hope Radio as Behnam Badie, M.D., director of the Brain Tumor Pro...
  • The whole is greater than the sum of its parts. It takes a village. No man is an island. Choose your aphorism: It’s a simple truth that collaboration usually is better than isolation. That’s especially true when you’re trying to introduce healthful habits and deliver health care to people at risk of disease and...
  • When Maryland Governor Larry Hogan announced earlier this week that he has the most common form of non-Hodgkin lymphoma, he was giving voice to the experience of more than 71,000 Americans each year. The announcement came with Hogan’s promise to stay in office while undergoing aggressive treatment for the...
  • The spine can be affected by many different kinds of tumors. Malignant, or cancerous, tumors can arise within the spine itself. Secondary spinal tumors, which are actually much more common, begin as cancers in another part of the body, such as the breast and prostate, and then spread, or metastasize, to the spi...
  • Although most cancer occurs in older adults, the bulk of cancer research doesn’t focus on this vulnerable and fast-growing population. City of Hope and its Cancer and Aging Research Team aim to change that, and they’re getting a significant boost from Professional Practice Leader Peggy Burhenn, R.N....
  • Liz Graef-Larcher’s first brain tumor was discovered by accident six years ago. The then-48-year-old with a long history of sinus problems and headaches had been sent for an MRI, and the scan found a lesion in her brain called a meningioma – a tumor that arises in the meninges, the layers of tissue that cover a...
  • The colon and rectum are parts of the body’s gastrointestinal system, also called the digestive tract. After food is digested in the stomach and nutrients are absorbed in the small intestine, the remaining material moves down into the lower large intestine (colon) where water and nutrients are absorbed. The low...
  • If there is one truism about hospital stays it is that patients want to get out. For many, however, the joy of being discharged is tempered by the unexpected challenges that recovery in a new setting may pose. Even with professional help, the quality of care and treatment that patients receive at City of Hope [...
  • Jana Portnow, M.D., associate director of the Brain Tumor Program at City of Hope, didn’t expect to specialize in treating brain tumors. But, early in her career, she undertook a year of research on pain management and palliative care and, in that program, got to know many patients with brain tumors. After that...
  • Ask any patient: Nurses are as pivotal in their care as doctors. They answer the call of a patient in the middle of the night, they hold the patient’s hand as he or she takes on yet another round of treatment and, in the best-case scenario, they wave goodbye as the patient leaves the hospital, […]
  • Many oncologists, not to mention their patients, might think that there’s no place for mathematical analysis in the treatment of cancer. They might think that all treatment decisions are based on unique factors affecting individual patients, with no connection to other patients and their treatment regimen...
  • Within three days in 2007, Stephanie Hosford, then 37, learned that she was pregnant with her long-awaited second child – and that she had triple-negative breast cancer. Soon afterward, Hosford discovered that she and her husband, Grant, had been approved to adopt a little girl from China.  After encountering m...