- Graduate School – University of Chicago, Pritzker School of Medicine - PhD
- Medical School – University of Chicago, Pritzker School of Medicine – MD
- Residency – Children’s Hospital Boston/Harvard Medical School – Pediatrics
- Fellowship – Children’s Hospital Boston/Dana-Farber Cancer Institute/Harvard Medical School - Pediatric Hematology/Oncology
Education & Training
NIH Grants: R01
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
- Wang H, Chauhan J, Hu A, Pendleton K, Yap JL, Sabato PE, Jones JW, Perri M, Yu J, Cione E, Kane MA, Fletcher S, Prochownik EV. Erratum: Disruption of Myc-Max Heterodimerization with Improved Cell-Penetrating Analogs of the Small Molecule 10074-G5. Oncotarget. 2018 Oct 12;9(80):35196. doi: 10.18632/oncotarget.26241. eCollection 2018 Oct 12. PubMed PMID: 30416689; PubMed Central PMCID: PMC6205554.
- Gu L, Zhu Y, Lin X, Li Y, Cui K, Prochownik EV, Li Y. Amplification of Glyceronephosphate O-Acyltransferase and Recruitment of USP30 Stabilize DRP1 to Promote Hepatocarcinogenesis. Cancer Res. 2018 Oct 15;78(20):5808-5819. doi: 10.1158/0008-5472.CAN-18-0340. Epub 2018 Aug 24. PubMed PMID: 30143522.
- Wang H, Dolezal JM, Kulkarni S, Lu J, Mandel J, Jackson LE, Alencastro F, Duncan AW, Prochownik EV. Myc and ChREBP transcription factors cooperatively regulate normal and neoplastic hepatocyte proliferation in mice. J Biol Chem. 2018 Sep 21;293(38):14740-14757. doi: 10.1074/jbc.RA118.004099. Epub 2018 Aug 7. PubMed PMID: 30087120; PubMed Central PMCID: PMC6153302.
- Goetzman ES, Prochownik EV. The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues. Front Endocrinol (Lausanne). 2018 Apr 12;9:129. doi: 10.3389/fendo.2018.00129. eCollection 2018. Review. PubMed PMID: 29706933; PubMed Central PMCID: PMC5907532.
- Li W, Cui K, Prochownik EV, Li Y. The deubiquitinase USP21 stabilizes MEK2 to promote tumor growth. Cell Death Dis. 2018 May 1;9(5):482. doi: 10.1038/s41419-018-0523-z. PubMed PMID: 29706623; PubMed Central PMCID: PMC5924753.
- Dolezal JM, Dash AP, Prochownik EV. Diagnostic and prognostic implications of ribosomal protein transcript expression patterns in human cancers. BMC Cancer. 2018 Mar 12;18(1):275. doi: 10.1186/s12885-018-4178-z. PubMed PMID: 29530001; PubMed Central PMCID: PMC5848553.
- Jackson LE, Kulkarni S, Wang H, Lu J, Dolezal JM, Bharathi SS, Ranganathan S, Patel MS, Deshpande R, Alencastro F, Wendell SG, Goetzman ES, Duncan AW, Prochownik EV. Genetic Dissociation of Glycolysis and the TCA Cycle Affects Neither Normal nor Neoplastic Proliferation. Cancer Res. 2017 Nov 1;77(21):5795-5807. doi: 10.1158/0008-5472.CAN-17-1325. Epub 2017 Sep 7. PubMed PMID: 28883002; PubMed Central PMCID: PMC5668145.
- Kulkarni S, Dolezal JM, Wang H, Jackson L, Lu J, Frodey BP, Dosunmu-Ogunbi A, Li Y, Fromherz M, Kang A, Santana-Santos L, Benos PV, Prochownik EV. Ribosomopathy-like properties of murine and human cancers. PLoS One. 2017 Aug 18;12(8):e0182705. doi: 10.1371/journal.pone.0182705. eCollection 2017. PubMed PMID: 28820908; PubMed Central PMCID: PMC5562309.