Jack F. Shern, M.D.

Lasker Clinical Research Scholar

Pediatric Oncology Branch


Building 10, Room 1-3750
Bethesda, MD 20892



Research Topics

Survival rates for childhood malignancies have been stagnant, in part due to a lack of a detailed understanding of the molecular mechanisms of action that drive these tumors. My group uses next generation genomic and molecular assays in an attempt to:

1. Detect and define the somatic lesions that drive tumorigenesis of rare and deadly pediatric tumors. In particular, we are interested in translocation events that produce fusion oncogenes of transcription factors. These events are the driving lesions in many of the difficult to treat pediatric sarcomas such as alveolar rhabdomyosarcoma and Ewing sarcoma. Interestingly, we have found that while these fusion oncogenes are often one of the few genetic rearrangements observed in within these tumors, they have profound effects on the transcriptional output of these cells.

2. Resolve underlying tumor heterogeneity and mechanisms of resistance that allow a tumor to progress or relapse after therapy. To accomplish this, we are using and developing novel droplet based methods to barcode and sequence and analyze the expression profile from thousands of cells in a single experiment.

3. Use high-throughput siRNA, small molecule and natural product drug screening to discover precision therapeutics designed to target a tumors underlying genetic or epigenetic drivers. The results of these studies are being rapidly translated into potential clinical trials within the Pediatric Oncology Branch.


After completing undergraduate studies at the University of Notre Dame, South Bend, Indiana, Dr. John 'Jack' Shern received his M.D. from the Medical College of Georgia in 2007. This was followed by his pediatric internship and residency training at the University of Chicago Comer Children's hospital, which he completed in 2010. He then joined the combined Pediatric Hematology and Oncology Fellowship training program at the National Cancer Institute, Pediatric Oncology Branch (POB) and Johns Hopkins University. In his fellowship, Dr. Shern worked under the mentorship of Dr. Javed Khan in the Center for Cancer Research's Genetics Branch to use next generation sequencing to profile the somatic changes which drive multiple pediatric solid tumors. Dr. Shern was then an Assistant Clinical Investigator in the POB and became an NIH Lasker Investigator in 2018.

Selected Publications

  1. Chen L, Shern JF, Wei JS, Yohe ME, Song YK, Hurd L, Liao H, Catchpoole D, Skapek SX, Barr FG, Hawkins DS, Khan J. Clonality and evolutionary history of rhabdomyosarcoma. PLoS Genet. 2015;11(3):e1005075.
  2. Shern JF, Chen L, Chmielecki J, Wei JS, Patidar R, Rosenberg M, Ambrogio L, Auclair D, Wang J, Song YK, Tolman C, Hurd L, Liao H, Zhang S, Bogen D, Brohl AS, Sindiri S, Catchpoole D, Badgett T, Getz G, Mora J, Anderson JR, Skapek SX, Barr FG, Meyerson M, Hawkins DS, Khan J. Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of alterations affecting a common genetic axis in fusion-positive and fusion-negative tumors. Cancer Discov. 2014;4(2):216-31.
  3. Long AH, Haso WM, Shern JF, Wanhainen KM, Murgai M, Ingaramo M, Smith JP, Walker AJ, Kohler ME, Venkateshwara VR, Kaplan RN, Patterson GH, Fry TJ, Orentas RJ, Mackall CL. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med. 2015;21(6):581-90.
  4. Shern JF, Yohe ME, Khan J. Pediatric Rhabdomyosarcoma. Crit Rev Oncog. 2015;20(3-4):227-43.
  5. Brohl AS, Solomon DA, Chang W, Wang J, Song Y, Sindiri S, Patidar R, Hurd L, Chen L, Shern JF, Liao H, Wen X, Gerard J, Kim JS, Lopez Guerrero JA, Machado I, Wai DH, Picci P, Triche T, Horvai AE, Miettinen M, Wei JS, Catchpool D, Llombart-Bosch A, Waldman T, Khan J. The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation. PLoS Genet. 2014;10(7):e1004475.

Related Scientific Focus Areas

This page was last updated on Thursday, September 7, 2023