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
  • We’ve all heard the mantra: Cancer screening saves lives. And it does, especially with colorectal cancer. Regular colonoscopies have been proven to reduce the risk of colorectal cancer death by up to 70 percent. Screening for colorectal cancer using the even simpler fecal occult blood tests has been found to re...
  • Pick up any biotech industry report and you’re guaranteed to come across one term repeatedly – CAR-T therapy. A fierce competition is now underway to bring CAR-T treatments to market – several companies (Juno, Novartis, Kite and Cellectis, to name a few) have major stakes in the race. I’ve found the CAR-T buzz ...
  • Patients undergoing treatment at City of Hope know they will be receiving the best medical care available, that their treatment will be delivered with compassion and that their care will extend to their families. “When we treat a patient here, we treat a family,” says Jo Ann S. Namm, child life manager and spec...
  • Did you know that colorectal cancer equally affects men and women? Or that it’s the third-leading cause of cancer death in the U.S.? Most important, did you know that colorectal cancer is very treatable and highly curable if detected early? If you didn’t know these facts, it’s time to learn. M...
  • To celebrate the beginning of Lunar New  Year 2015, City of Hope honored not just a new lunar calendar, but also the diversity of the community it serves. On Jan. 21, as tens of thousands of people celebrated Lunar New Year (and the arrival of the Year of the Ram) in the streets of L.A.’s Chinatown, City of [&#...
  • The breakthroughs that have revolutionized cancer treatment, transforming cancer in many cases to a very manageable and even curable disease, started out as just ideas. “I will often tell patients there’s no therapy we’re using to help them that wasn’t derived from somebody’s idea in some laboratory, working la...
  • The prostate cancer screening debate, at least as it relates to regular assessment of prostate specific antigen levels, is far from over. The U.S. Preventive Services Task Force recommended against routine PSA screening for prostate cancer in 2012, maintaining that the routine use of the PSA blood test does mor...
  • Cancer patients should get more than medical treatment. They should get comprehensive, evidence-based care that addresses their full range of needs. That kind of patient-focused care is City of Hope’s specialty. Under the guidance of Dawn Gross, M.D., Ph.D., the new Arthur M. Coppola Family Chair in Suppo...
  • Think twice before tossing out those hormone replacement pills. Although a new Lancet study suggests that hormone replacement therapy could increase a woman’s risk of ovarian cancer, a City of Hope expert urges women to keep this news in perspective. Hormone replacement therapy is prescribed to help allev...
  • Don’t know what to take, or send, that friend of yours in the hospital? Try a paper plate — filled not with cookies or sweets, but an image of yourself. Ilana Massi, currently undergoing treatment at City of Hope for acute myeloid leukemia, can vouch for the power of such a gift. She’s surrounded herself [̷...
  • With precision medicine now a national priority, City of Hope has joined a novel research partnership designed to further understanding of cancer at the molecular level, ultimately leading to more targeted cancer treatments. The Oncology Research Information Exchange Network, or ORIEN, is the world’s larg...
  • The spinal cord is an integral part of the human body, connecting the brain to everything else. So when a tumor grows on the spine, any messages that the brain tries to send to the rest of the body are interrupted, making everyday tasks — such as walking — more difficult. This year an estimated 22,850 […]
  • Each year, thousands of patients with hematologic malignancies undergo allogeneic stem cell transplantation (that is, they receive a donor’s stem cells), offering them a chance at cure. Graft-versus-host disease is a potentially deadly complication of this therapy and occurs in approximately 25 to 60 perc...
  • Bertram Yuh, M.D., assistant clinical professor in the Division of Urology and Urologic Oncology at City of Hope, offers his perspective on the benefits of surgery for aggressive prostate cancer. For men walking out of the doctor’s office after a diagnosis of cancer, the reality can hit like a ton of bricks. Th...
  • Although many Hispanic women face a high risk of mutations in the BRCA1 and BRCA2 genes – increasing their risk of breast and ovarian cancer – screenings for these mutations can be prohibitively expensive in Mexico and other Latin American countries. As a result, too many women don’t get the information t...