Edward Prochownik, MD, PhD

Current research in my laboratory focuses on the following major areas.

The role of the Myc network in cellular energy metabolism. Rapidly dividing tumor cells must increase their production of ATP in order to provide the necessary building blocks to maintain their increased biomass. Alterations in cellular metabolism thus occur in order to provide these requisite anabolic precursors.  We are interested in the means by which Myc and proteins that collaborate with Myc alter aerobic glycolysis, mitochondrial structure, glutaminolysis and fatty avid oxidation. We have recently shown that Myc exerts profound effects on these processes, particularly in conjunction with other proteins that sense and respond to intracellular energy levels such as carbohydrate response element binding protein (ChREBP) and AMP-dependent protein kinase (AMPK).  We are currently employing a variety of mouse knockout models to define the functional relationships among these pathways and how they cross-talk with one another to balance energy production and utilization to maintain the growth of tumor cells.
In vivo models of hepatocellular carcinogenesis. We currently work with several mouse models that recapitulate the most common pediatric and adult liver cancers, namely, hepatoblastoma and hepatocellular carcinoma (HCC). In the first case, we are able to obtain rapid and robust hepatoblastoma generation via the over-expression of the b-catenin and YAP oncoproteins in mouse liver. Transcriptional profiling has provided new insights into how these two oncoproteins induce cancer.  These alterations include up-regulation of the Myc gene, changes in ribosomal biogenesis and carbohydrate and lipid metabolism and the suppression of tumor suppressor genes.  The second model of HCC is particularly interesting as it allow for tumor induction simply by over-expressing Myc in the liver under conditions that allow for its induction and subsequent silencing at any time. Tumor growth and progression require the continuous expression of Myc and regression occurs within days of its being silenced.  Moreover, tumors recur following the re-expression of Myc.  This model is providing the means to follow the molecular, biochemical and metabolic changes that occur over the course of tumor evolution as the liver progresses from a normal stateàpre-neoplasticàgrowing tumoràregressing tumoràrecurrent tumor, all of which occur over the course of ~ 4 months