SIGNALING PATHWAYS IN CANCER
ACCEPTING APPLICATIONS FOR POSTDOCTORAL POSITION
VISION & FOCUS
The major goal of the Emerling lab is to understand the role of phosphoinositide kinases, in particular the phosphatidylinositol-5-phosphate 4-kinases (PI5P4Ks), in tumor cell growth and metabolism. Our recent studies, based on gene deletion in mice, reveal that these enzymes control glucose homeostasis, insulin sensitivity and susceptibility to tumor formation in p53 mutant backgrounds, raising the possibility that inhibitors of these ‘druggable’ enzymes could be efficacious in treating cancer, in particular p53 mutant cancers. Our work proposes to understand the biochemical basis for the function of these enzymes and to further validate them as targets for pharmaceutical intervention in cancer.
Triple negative breast cancer (TNBC) accounts for 15-20% of breast cancers. Women with TNBC are three times more likely to experience death compared to other subtypes. Mutations in the tumor suppressor gene TP53 (encoding p53) are found in the vast majority of TNBC. Although TP53 mutations are found frequently in TNBC, it is difficult to target p53-deficiency with drugs. The poor prognosis of TNBC can be attributed to the lack of effective targeted therapy. We have shown that the PI5P4K enzymes are crucial for the growth of breast cancers that have genetic aberrations in p53. Using preclinical studies in novel genetically engineered breast cancer mouse models and in human breast cancer cells we are investigating whether targeting these enzymes will be an effective therapy for TP53 mutant breast cancers, especially the TNBC subgroup where targeted therapies have not been effective.
The bulk of cellular PI-4,5-P2 is generated at the plasma membrane by the canonical pathway in which a 5-kinase (PI4P5K) converts PI-4-P to PI-4,5-P2. The PI5P4K enzymes provide an alternative pathway for generating PI-4,5-P2 at intracellular locations, such as the nucleus, lysosomes and autophagosomes, by phosphorylating PI-5-P. We have demonstrated that the PI5P4K enzymes play critical roles in mediating changes in metabolism in response to cellular stress. Our working model is that the PI5P4K pathway is a stress response pathway that is necessary for the maintenance of glucose metabolism, autophagy, and transcription under conditions of severe stress or upon loss of TP53. Current aims in the Emerling lab are to dissect the role(s) of the PI5P4K enzymes in these metabolic signaling pathways.
MEET THE EMERLING LAB TEAM
BROOKE EMERLING Ph.D.
Brooke received her BA from the University of California, Santa Cruz and her Ph.D. from Northwestern University. As a Ph.D. student in the laboratory of Navdeep Chandel, Brooke identified and characterized novel signaling pathways that regulate the transcription factor hypoxia inducible factor-1. Upon completion of her Ph.D, Brooke joined the laboratory of Lewis Cantley at Harvard Medical School. There she discovered that the loss of function of the PI5P4Ks resulted in synthetic lethality with p53 loss and began to elucidate the role of the PI5P4K family of enzymes in cancer metabolism. After she completed her postdoctoral fellowship at Harvard Medical School, Brooke became an Instructor of Cancer Biology in Medicine at Weill Cornell Medicine where she continued her research on lipid kinase signaling and cancer metabolism. In August 2016, Brooke joined the faculty at SBP Medical Discovery Institute as an Assistant Professor in the Cancer Metabolism and Signaling Networks Program.
Ryan recieved his BS in Biology from the University of Pittsburgh. Before joining the Emerling lab in 2016, Ryan was a research technician in the Cantley Lab at Weill Cornell Medicine. As a graduate student in the Emerling lab, he is currently focusing on uncovering the mechanism by which the PI5P4K enzymes act as compensatory metabolic sensors in p53 mutant cancers. In his spare time, he enjoys golf, tennis, and attempting to write the next Hugo award winning sci-fi novel.
Archna received her MS in Molecular Biology from the University of Madras (2008) and her Ph.D. from National University of Singapore (2013) where she worked on RhoGTPase signaling in cell migration. Before joining the Emerling Lab in 2017, she was a postdoc at UC Irvine. Archna's research interests include understanding how the PI5P4K enzymes regulate intricate aspects of cell biology and their role(s) in metabolism and cancer. Outside the lab, Archna enjoys books, beaches, and traveling.
Lavinia received her master's degree in Biotechnology from the University of Iasi, Romania (2010) and her PhD in Neuroscience from the University of Strasbourg, France (2014). Her PhD research focused on pre-symptomatic metabolic alterations in muscle tissue in a mouse model for amyotrophic lateral sclerosis. Before joining the Emerling Lab, she was a post-doc at The Scripps Research Institute where she studied fat metabolism and neuroendocrine signaling in C.elegans in Dr. Srinivasan's lab. Currently she is studying the role of PI5P4K enzymes in metabolic homeostasis and pathology. In her free time, Lavinia enjoys reading, photography, learning new languages, and hiking.
Vivian is currently a student at UC San Diego and on track to receive her BS in Human Biology in June 2020. As an aspiring pre-med, she joined the Emerling Lab with hopes in gaining more insight on the variety of facets of medicine. During her free time, Vivian enjoys reading, biking, and exploring new “foodie” places.
Sarah received her BA in Business Marketing from San Diego State University and a Bachelor of Science in Business Administration from the University of Phoenix. Prior to joining SBP she was a Marketing Manager at the Institute for Health Maintenance. Sarah was born and raised in Southern California. She spends most of her free time with her 2-year-old daughter and husband enjoying all that San Diego as to offer. She is a certificated Pilates instructor and continues to practice Pilates today.
Ann Pham (Research Associate, 2017-2018) - Currently: Research Associate, Organovo Holdings, Inc.
Oscar Donosa (Undergraduate student, 2017) - Currently: UCSD undergraduate