Edward V. Prochownik, MD, PhD

  • Paul C. Gaffney Professor of Pediatrics
  • Professor of Microbiology and Molecular Genetics

Administrative Assistant: Carla Clarke

1. The role of the Myc oncoprotein 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 serve to provide these requisite anabolic precursors. The c-Myc (Myc) oncoprotein is deregulated in >50% of all human cancers.  We are interested in the means by which Myc and proteins that collaborate with Myc alter aerobic glycolysis, mitochondrial structure, glutaminolysis and fatty acid 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.  These include members of the “alternate” or “parallel” Myc pathway comprised of members such as ChREBP, MondoA, Mlx and Mnt.  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.

 

2. The role of the “Extended Myc network’ in promoting wellness and survival. In addition to its well-known role in cancer, Myc also plays important roles in normal cellular functions including proliferation, differentiation, the regulation of metabolism and ribosomal biogenesis. However, because total body loss of myc is embryonic lethal, it has been impossible to gain insight into its role more global role.  We have recently developed a strain of mice in which body-wide knockout of myc can be achieved while preserving survival. We are documenting the developmental and life-long consequences of this loss which thus far include significant effects on metabolism, strength and aging. A similar approach has allowed for a knockout of Mlx, leading to the functional inactivation of the Myc-like proteins MondoA and ChREBP. The phenotypes and life-long consequences of mlx knockout are also being studied as they are for myc knockouts.  Finally, the generation of a double myc x mlx mouse strain will enable us to study the consequences of inactivating the entire Extended Myc Network on long-term health, welness and longevity.

 

3. 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 obtain rapid and robust hepatoblastoma generation via the over-expression of patient-derived mutant forms 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 inhibition of tumor suppressor genes. The model of HCC is particularly interesting as it allows for conditional tumor induction simply by over-expressing Myc in the liver. Tumor growth and progression require the continuous expression of Myc and regression occurs within days of its silencing.  Moreover, tumors recur following Myc re-expression.  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 state->pre-neoplastic->growing tumor->regressing tumor->recurrent tumor, all of which occur over the course of ~ 4 months. 

 

 

Education & Training

  • BA, Biology, Johns Hopkins University, 1972
  • PhD, Pathology/Virology, University of Chicago, 1977
  • MD, University of Chicago-Pritzker School of Medicine, 1978
  • Internship in Pediatrics, Boston Children's Hospital, 1978-1979
  • Junior Assistant Resident in Pediatrics, Boston Children's Hospital, 1979-1980
  • Clinical Fellow in Pediatric Hematology-Oncology, The Children's Hospital and Dana Farber Cancer Institute-Harvard Medical School, 1980-1981
  • Research Fellow in Pediatric Hematology-Oncology, The Children's Hospital and Dana Farber Cancer Institute-Harvard Medical School, 1981-1983

Selected Publications

Academic and Research Interests

  • Cancer Genetics
  • Hepatoblastoma
  • Hepatocellular Carcinoma
  • Tumor Supressors
  • Myc Oncogene
  • Cancer Metabolism
  • Cancer and Aging
  • Pediatric Cancer

Research Grants

1RO1 CA174713, Control of Metabolism and Energy-Sensing Pathways by c-Myc, Funding Agency: NIH, PI, 07/01/14-6/30/19, 10% effort, $1,638,864

Project 1: Pre-Clinical and Clinical Imaging and Treatment of Multiple Myeloma with C-Myc-Max Nanoparticles, NIH, PI: Gregory Lanza, MD (Washington Univ. School of Medicine), 9/1/15-8/31/20, 10% effort, $396,705

522000 Ribosomopathy-like properties of Cancers, Hyundai Hope on Wheels (Hyundai Corp.), PI, 6/1/17-5/31/19, 10% effort, $250,000

Patient-Derived NFE2L2/NRF2 Mutations Promote Aggressive Forms of Hepatoblastoma, The V Foundation, PI, 9/1/20-8/31/21, 10% effort, $150,000

CV