Faculty

Grzegorz Nalepa, M.D, Ph. D

Grzegorz Nalepa, M.D, Ph. D

Assistant Professor of Pediatrics

Phone: 317-944-2143
Email: gnalepa@iu.edu
Address:
705 Riley Hospital Drive, ROC 4340
Indianapolis, IN 46202 

Bio

Specialty

Pediatric Hematology Oncology
Medical and Molecular Genetics 

Areas of Interest

Fanconi anemia and other bone marrow failure syndromes, cancer genetics and cancer predisposition syndromes, genomic instability, mitosis, aneuploidy, chromosome segregation, MDS, acute leukemias, personalized therapeutics

Bio

Dr. Nalepa is a physician-scientist with clinical and research expertise in bone marrow failure syndromes and cancer genetics. He leads a comprehensive pediatric bone marrow failure clinic at Riley Hospital for Children (for patient referral, e-mail rileybmf@iu.edu). His laboratory employs functional genomics and superresolution imaging to understand the mechanistic origins of genomic instability in Fanconi anemia and other bone marrow failure/cancer predisposition syndromes to identify novel personalized therapeutic strategies.

Education

1999 M.D. , Silesian School of Medicine
2001-2005 Ph.D. , Baylor College of Medicine
2005-2006 Postdoctoral fellow, Harvard Medical School
2006-2009 Pediatric Residency, IU School of Medicine
2009-2012 Pediatric hematology-oncology Fellowship, IU School of Medicine

Honors & Awards

  • 2012 SPR David G. Nathan Award in Basic Research
  • 2011, 2013 Red Shoes Award, Riley Hospital for Children
  • 2006–2012 Morris Green Academic Scholarship, IU School of Medicine
  • 2004 The Claude W. Smith Fellowship Award for Outstanding Research Performance
  • 2001 The Professor John F. Trentin Scholarship Award for Academic Excellence
  • 2000 Rockwell Scholarship Award
  • 1999 The Dean's Award for Best Medical Graduate
  • 1997-1998 Polish Ministry of Health Outstanding Medical Student Award

Clinical

Riley Outpatient Center
705 Riley Hospital Drive
Indianapolis, IN 46202
317-944-2143 phone
317-944-3107 fax


Current Research

Our group is interested in understanding the molecular mechanisms leading to genomic instability and carcinogenesis through abnormal cell division in Fanconi anemia (FA) as well as other bone marrow failure and cancer predisposition syndromes. We have found that loss of the Fanconi signaling network promotes chromosomal instability through weakened spindle assembly checkpoint and error-prone mitosis. We are further exploring the in vivo and ex vivo impact of mitotic aberrations due to inactivation of FA signaling on carcinogenesis using a wide battery of strategies, including generation and characterization of novel preclinical mouse models of FA, high-throughput functional genomics and superresolution microscopy. We hope our work will lead to identification of novel, rational therapeutic targets for Fanconi anemia and cancers that harbor somatic inactivation of the FA pathway.

Our laboratory also pursues a systematic mechanistic evaluation of several protein and small-molecule phosphatases identified through our high-throughput siRNA screens aimed to identify genes essential for mitotic chromosome segregation, centrosome maintenance and prevention of aneuploidy. We prioritize our genes of interests according to their independently discovered role as candidate tumor suppressors and oncogenes in human cancers. We hope our work will clarify the mechanisms of genomic instability resulting from dysregulation of these phosphosignaling pathways and open new inroads towards personalized therapeutics.

Dr. Nalepa serves as the director of Barth Syndrome Research Fund at Riley Childrens Foundation. Dr. Nalepa’s lab has received funding from NIH, ACS and IU School of Medicine.


Publications

Fanconi anemia signaling network regulates spindle assembly checkpoint. Nalepa G, Enzor R, Sun Z, Marchal C, Park SJ, Yang Y, Tedeschi L, Kelich S, Hanenberg H, Clapp DW.   J Clin Invest 2013; 123: 3839-3847.

Tumor suppressor CDKN3 controls mitosis. Nalepa G, Barnholtz-Sloan J, Enzor R, Dey D, Gehlhausen J, Lehmann A, Khan S, Yang Y, Yang X, Chen S, Guan X, Chen Y, Renbarger J, Yang FC, Parada LF, Clapp DW.  J Cell Biol 2013; 201:997-1012.

Fanconi anemia and the cell cycle: new perspectives on aneuploidy. Nalepa G and Clapp DW. F1000Prime Rep. 2014; 6:23. ECollection 2014.

Normal hematopoiesis and neurofibromin-deficient myeloproliferative disease require Erk. Staser K, Park SJ, Rhodes S, Zeng Y, He Y, Shew M, Gehlhausen J, Cerabona D, Menon K, Chen S, Sun Z, Yuan J, Ingram D, Nalepa G, Yang FC, Clapp DW.  J Clin Invest. 2013 Jan 2;123(1):329-34. doi: 10.1172/JCI66167. Epub 2012 Dec 10.

Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial. Robertson KA, Nalepa G, Yang FC, Bowers DC, Ho CY, Hutchins GD, Croop JM, Vik TA, Denne SC, Parada LF, Hingtgen CM, Walsh LE, Yu M, Pradhan KR, Edwards-Brown MK, Cohen MD, Fletcher JW, Travers JB, Staser KW, Lee MW, Sherman MR, Davis CJ, Miller LC, Ingram DA, Clapp DW.  Lancet Oncol. 2012 Dec;13(12):1218-24. doi: 10.1016/S1470-2045(12)70414-X. Epub 2012 Oct 23.

Drug discovery in the ubiquitin-proteasome system. Nalepa G, Rolfe M, Harper JW. Nat Rev Drug Discov. 2006 Jul;5(7):596-613. 

Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, McDonald ER 3rd, Li MZ, Hannon GJ, Sorger PK, Kirschner MW, Harper JW, Elledge SJ. Nature. 2007 Apr 19; 446(7138):876-81.

The tumor suppressor CYLD regulates entry into mitosis. Stegmeier F, Sowa ME, Nalepa G, Gygi SP, Harper JW, Elledge SJ. Proc Natl Acad Sci U S A. 2007 May 22; 104(21):8869-74. Epub 2007 May 10. PMCID: PMC1867381

A functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling. Draviam VM, Stegmeier F, Nalepa G, Sowa ME, Chen J, Liang A, Hannon GJ, Sorger PK, Harper JW, Elledge SJ. Nat Cell Biol. 2007 May;9(5):556-64. Epub 

Genetic disruption of both Fancc and Fancg in mice recapitulates the hematopoietic manifestations of Fanconi anemia. Pulliam-Leath AC, Ciccone SL, Nalepa G, Li X, Si Y, Miravalle L, Smith D, Yuan J, Li J, Anur P, Orazi A, Vance GH, Yang FC, Hanenberg H, Bagby GC, Clapp DW. Blood. 2010 Oct 21; 116(16):2915-20. Epub 2010 Jul 6. PMCID: PMC2974601