Patrick J. Grohar, MD, PhD

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Patrick J. Grohar, MD, PhD, is an attending physician with the Cancer Center and the Director of Translational Research with the Center of Childhood Cancer Research at Children's Hospital of Philadelphia.

Locations: Main Campus

Appointments and Referrals: 1-800-TRY-CHOP (1-800-879-2467)

Background

Patrick J. Grohar, MD, PhD is a pediatric oncologist and physician-scientist focused on the development of novel molecularly targeted therapies for pediatric solid tumors. After completing a B.S. in Chemistry at Villanova University, Dr. Grohar went on to complete both the MD and PhD degrees at Wayne State University. He completed pediatric training and a fellowship in hematology-oncology at Johns Hopkins University and the National Institutes of Health. He held faculty appointments at Vanderbilt University and the Van Andel Institute prior to his arrival at CHOP as an Associate Professor of Pediatrics and director of translational research within the Center for Childhood Cancer Research.

The Grohar Laboratory employs a bench to bedside and back again approach to develop targeted therapies for pediatric solid tumors. The laboratory has focused primarily on the therapeutic targeting of the EWS-FLI1 transcription factor for Ewing sarcoma.  EWS-FLI1 is the clear oncogenic driver of Ewing sarcoma but a challenging drug target. Our laboratory has employed a number of complementary approaches to directly target EWS-FLI1, develop targeted combination therapies and identify novel drug targets. We have a number of studies in various stages of clinical translation. More recently, we have employed similar approaches to develop targeted therapies focused on other pediatric solid tumors that are dependent on similar drug targets and are characterized by few other somatic mutations.

Dr. Grohar is recognized for his work in Ewing sarcoma. He holds leadership positions within the Center for Childhood Cancer Research at CHOP and nationally within the Children’s Oncology Group. He is the Vice-Chair for Biology of the Bone Tumor Committee, Co-Chair of Combined Sarcoma Biology Committee and Chair of the Ewing Sarcoma Biology Committee. He is a Principle Investigator with the Sarcoma Alliance for Research through Collaboration. He serves as an ad hoc journal for multiple journals, the National Institutes of Health and for the Cancer Prevention Research Institute of Texas (CPRIT).

Education and Training

Medical School

MD - Wayne State University, Detroit, MI

Residency

Pediatrics, Research Track - Johns Hopkins University, Baltimore, MD

Fellowship

Hematology/Oncology -  Johns Hopkins University, Baltimore, MD / National Institutes of Health, Bethesda, MD (Chief Fellow)

Board Certification

Pediatric Hematology/Oncology
Pediatrics

Undergraduate Degree

BS - Chemistry, Villanova University, Villanova, PA

Graduate Degree

PhD in Chemistry and Biochemistry - Wayne State University, Detroit, MI

Titles and Academic Titles

Attending Physician

Senior Research Scientist

Director, Translational Research, Center of Childhood Cancer Research

Associate Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

Conditions Treated

Departments and Services

Publications

Papers

2020

Flores G, Everett JH, Boguslawski EA, Oswald BM, Madaj ZB, Beddows I, Dikalov S, Adams M, Klumpp-Thomas CA, Kitchen-Goosen SM, Martin SE, Caplen NJ, Helman LJ, Grohar PJ. CDK9 Blockade Exploits Context-Dependent Transcriptional Changes to Improve Activity and Limit Toxicity of Mithramycin for Ewing Sarcoma. Mol Cancer Ther. 2020 Mar 3. pii: molcanther.0775.2019. doi: 10.1158/1535-7163.MCT-19-0775. [Epub ahead of print]

2019

Sissung TM, Huang PA, Hauke RJ, McCrea EM, Peer CJ, Barbier RH, Strope JD, Ley AM, Zhang M, Hong JA, Venzon D, Jackson JP, Brouwer KR, Grohar P, Glod J, Widemann BC, Heller T, Schrump DS, Figg WD. Severe Hepatotoxicity of Mithramycin Therapy Caused by Altered Expression of Hepatocellular Bile Transporters. Mol Pharmacol. 2019 Aug;96(2):158-167. doi: 10.1124/mol.118.114827. Epub 2019 Jun 7. PMID: 31175181

Bailey, K. M., Cost, C. R., Davis, I. J., Glade-Bender, J., Grohar, P. J., Houghton, P. J., Isakoff, M. S., Stewart, E., Laack, N., Yustein, J. T., Reed, D. R., Janeway, K. A., Gorlick, R., Lessnick, S. L., DuBois, S. G., Hingorani, P.: Emerging novel agents for patients with advanced Ewing sarcoma: a report from the Children's Oncology Group (COG) new agents for Ewing sarcoma task force. F1000Res. 2019 Apr 15;8. pii: F1000 Faculty Rev-493. doi: 10.12688/f1000research.18139.1. eCollection 2019.

Harlow ML, Chasse MH, Boguslawski EA, Sorensen KM, Gedminas JM, Kitchen-Goosen SM, Rothbart SB5, Taslim C6, Lessnick SL, Peck AS, Madaj ZB, Bowman MJ, Grohar PJ: Trabectedin Inhibits EWS-FLI1 and Evicts SWI/SNF from Chromatin in a Schedule Dependent Manner. Clin Cancer Res. 2019 Feb 5. doi: 10.1158/1078-0432.CCR-18-3511. [Epub ahead of print]

2017

Grohar PJ, Janeway KA, Mase LD, Schiffman JD. 2017. Advances in treatment of pediatric sarcomas.  Am Soc Clin Oncol Educ Book 37:725–735.

Grohar Patrick J, Glod John, Peer Cody J, Sissung Tristan M, Arnaldez Fernanda I, Long Lauren, Figg William D, Whitcomb Patricia, Helman Lee J, Widemann Brigitte C: A phase I/II trial and pharmacokinetic study of mithramycin in children and adults with refractory Ewing sarcoma and EWS-FLI1 fusion transcript. Cancer chemotherapy and pharmacology 80(3): 645-652, Sep 2017.

Pridgeon Matthew G, Grohar Patrick J, Steensma Matthew R, Williams Bart O: Wnt Signaling in Ewing Sarcoma, Osteosarcoma, and Malignant Peripheral Nerve Sheath Tumors. Current osteoporosis reports 15(4): 239-246, Aug 2017.

2016

Herzog J, von Klot-Heydenfeldt F, Jabar S, Ranft A, Rossig C, Dirksen U, Van den Brande J, D’Incalci M, von Leuttichau I, Grohar PJ, Berdel WE, Burdach S. 2016. Trabectedin followed by irinotecan can stabilize disease in advanced translocation-positive sarcomas. Sarcoma.

Kovar H, Amatruda J, Brunet E, Burdach S, Cidre-Aranaz F, de Alava E, Dirksen U, van der Ent W, Grohar PJ, Grünewald TG, Helman L, Houghton P, Iljin K, Korsching E, Ladanyi M, Lawlor E, Lessnick S, Ludwig J, Meltzer P, Metzler M, Mora J, Moriggl R, Nakamura T, Papamarkou T, Radic Sarikas B, Rédini F, Richter GH, Rossig C, Schadler K, Schäfer BW, Scotlandi K, Sheffield NC, Shelat A, Snaar-Jagalska E, Sorensen P, Stegmaier K, Stewart E, Sweet-Cordero A, Szuhai K, Tirado OM, Tirode F, Toretsky J, Tsafou K, Üren A, Zinovyev A, Delattre O. 2016. The second European interdisciplinary Ewing sarcoma research summit—A joint effort to deconstructing the multiple layers of a complex disease. Oncotarget 7:8613–8624.

Harlow Matt L, Maloney Nichole, Roland Joseph, Guillen Navarro Maria Jose, Easton Matthew K, Kitchen-Goosen Susan M, Boguslawski Elissa A, Madaj Zachary B, Johnson Ben K, Bowman Megan J, D'Incalci Maurizio, Winn Mary E, Turner Lisa, Hostetter Galen, Galmarini Carlos María, Aviles Pablo M, Grohar Patrick J: Lurbinectedin Inactivates the Ewing Sarcoma Oncoprotein EWS-FLI1 by Redistributing It within the Nucleus. Cancer research 76(22): 6657-6668, Nov 2016.

Herzog J, von Klot-Heydenfeldt F, Jabar S, Ranft A, Rossig C, Dirksen U, Van den Brande J, D'Incalci M, von Luettichau I, Grohar P J, Berdel W E, Burdach St: Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity. Sarcoma Page: 7461783, Oct 24 2016 Notes: Epub only.

Osgood Christy L, Tantawy Mohammed N, Maloney Nichole, Madaj Zachary B, Peck Anderson, Boguslawski Elissa, Jess Jennifer, Buck Jason, Winn Mary E, Manning H Charles, Grohar Patrick J: F-FLT Positron Emission Tomography (PET) is a Pharmacodynamic Marker for EWS-FLI1 Activity and Ewing Sarcoma. Scientific reports 6(1): 33926, Sep 2016.

Osgood Christy L, Maloney Nichole, Kidd Christopher G, Kitchen-Goosen Susan, Segars Laura, Gebregiorgis Meti, Woldemichael Girma M, He Min, Sankar Savita, Lessnick Stephen L, Kang Min, Smith Malcolm, Turner Lisa, Madaj Zachary B, Winn Mary E, Núñez Luz-Elena, González-Sabín Javier, Helman Lee J, Morís Francisco, Grohar Patrick J: Identification of Mithramycin Analogues with Improved Targeting of the EWS-FLI1 Transcription Factor. Clinical cancer research : an official journal of the American Association for Cancer Research 22(16): 4105-18, Aug 2016.

Caropreso Vittorio, Darvishi Emad, Turbyville Thomas J, Ratnayake Ranjala, Grohar Patrick J, McMahon James B, Woldemichael Girma M: Englerin A Inhibits EWS-FLI1 DNA Binding in Ewing Sarcoma Cells. The Journal of biological chemistry 291(19): 10058-66, May 2016.

Grohar Patrick J, Kim Suntae, Rangel Rivera Guillermo O, Sen Nirmalya, Haddock Sara, Harlow Matt L, Maloney Nichole K, Zhu Jack, O'Neill Maura, Jones Tamara L, Huppi Konrad, Grandin Magdalena, Gehlhaus Kristen, Klumpp-Thomas Carleen A, Buehler Eugen, Helman Lee J, Martin Scott E, Caplen Natasha J: Functional Genomic Screening Reveals Splicing of the EWS-FLI1 Fusion Transcript as a Vulnerability in Ewing Sarcoma. Cell reports 14(3): 598-610, Jan 2016.

2015

Tancredi R, Zambelli A, DaPrada G A, Fregoni V, Pavesi L, Riccardi A, Burdach S, Grohar P J, D'Incalci M: Targeting the EWS-FLI1 transcription factor in Ewing sarcoma. Cancer chemotherapy and pharmacology 75(6): 1317-20, Jun 2015.

2014

Grohar Patrick J, Segars Laure E, Yeung Choh, Pommier Yves, D'Incalci Maurizio, Mendoza Arnulfo, Helman Lee J: Dual targeting of EWS-FLI1 activity and the associated DNA damage response with trabectedin and SN38 synergistically inhibits Ewing sarcoma cell growth. Clinical cancer research : an official journal of the American Association for Cancer Research 20(5): 1190-203, Mar 2014.

2013

Yeung C L, Ngo V N, Grohar P J, Arnaldez F I, Asante A, Wan X, Khan J, Hewitt S M, Khanna C, Staudt L M, Helman L J: Loss-of-function screen in rhabdomyosarcoma identifies CRKL-YES as a critical signal for tumor growth. Oncogene 32(47): 5429-38, Nov 2013.

Grohar Patrick J, Helman Lee J: Prospects and challenges for the development of new therapies for Ewing sarcoma. Pharmacology & therapeutics 137(2): 216-24, Feb 2013.

2011

Grohar PJ, Griffin LB, Yeung C, Chen QR, Pommier Y, Khanna C, Khan J, Helman LJ. 2011. Ecteinascidin 743 (ET-743) interferes with the activity of EWS-FLI1 in Ewing’s sarcoma cells.  Neoplasia 13(2):145–153.

Grohar Patrick J, Woldemichael Girma M, Griffin Laurie B, Mendoza Arnulfo, Chen Qing-Rong, Yeung Choh, Currier Duane G, Davis Sean, Khanna Chand, Khan Javed, McMahon James B, Helman Lee J: Identification of an inhibitor of the EWS-FLI1 oncogenic transcription factor by high-throughput screening. Journal of the National Cancer Institute 103(12): 962-78, Jun 2011.

Grohar Patrick J, Griffin Laurie B, Yeung Choh, Chen Qing-Rong, Pommier Yves, Khanna Chand, Khan Javed, Helman Lee J: Ecteinascidin 743 interferes with the activity of EWS-FLI1 in Ewing sarcoma cells. Neoplasia (New York, N.Y.) 13(2): 145-53, Feb 2011.

2007

Wan X, Harkavy B, Shen N, Grohar P, Helman L J: Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism. Oncogene 26(13): 1932-40, Mar 2007.

2004

Ge Yubin, Jensen Tanya L, Stout Mark L, Flatley Robin M, Grohar Patrick J, Ravindranath Yaddanapudi, Matherly Larry H, Taub Jeffrey W: The role of cytidine deaminase and GATA1 mutations in the increased cytosine arabinoside sensitivity of Down syndrome myeloblasts and leukemia cell lines. Cancer research 64(2): 728-35, Jan 2004.

2001

Schroeder M C, Hamby J M, Connolly C J, Grohar P J, Winters R T, Barvian M R, Moore C W, Boushelle S L, Crean S M, Kraker A J, Driscoll D L, Vincent P W, Elliott W L, Lu G H, Batley B L, Dahring T K, Major T C, Panek R L, Doherty A M, Showalter H D: Soluble 2-substituted aminopyrido[2,3-d]pyrimidin-7-yl ureas. Structure-activity relationships against selected tyrosine kinases and exploration of in vitro and in vivo anticancer activity. Journal of medicinal chemistry 44(12): 1915-26, Jun 2001.

2000

Meroueh M, Grohar P J, Qiu J, SantaLucia J, Scaringe S A, Chow C S: Unique structural and stabilizing roles for the individual pseudouridine residues in the 1920 region of Escherichia coli 23S rRNA. Nucleic acids research 28(10): 2075-83, May 2000.

1999

Grohar, P.J., Chow, C.S. : A practical synthesis of the modified RNA nucleoside pseudouridine. Tetrahedron Lett 40(1): 2049 - 2052, Mar 1999.

Books

Chapters

2019

Dirksen, U., Grohar, P.J.,DuBois, S., Davidson, D.,Hogendoorn, P.C.W., Lessnick, S.L.: Ewing Sarcoma. Pediatric Oncology. Pizzo and Poplack (eds.). Page: In press, 2019.

Posters and Presentations

2019

Gedminas J.M., Boguslawski E., Kitchen-Goosen S.M., Chasse M.H., Beddows I., Grohar P.J.: Lurbinectedin targets the EWS-WT1 transcription factor in desmoplastic small round cell tumor. Peer Reviewed Poster Presentation, Annual meeting of the American Society of Pediatric Hematology-Oncology, New Orleans, LA May 2019.

Flores, G., Kitchen-Goosen, S., Oswald, B.M., Boguslawski, E.A., Adams, M., Beddows, I., Madaj, Z.B., Grohar, P.J.: Mithramycin impedes EWS-FLI1 driven transcription by preventing target promoter clearance. Peer reviewed Poster Presentation at the Annual Meeting of the American Association for Cancer Research, Atlanta GA April 2019 Notes: AACR Minority Scholar-in-Training *Award.

Gedminas J.M., Boguslawski E., Kitchen-Goosen S.M., Chasse M.H., Beddows I., Grohar P.J.: Lurbinectedin inhibits the expression of EWS-WT1 in desmoplastic small round cell tumor. Peer Reviewed Poster Presentation Invited for an Oral Presentation at the 18th Annual State of Michigan Pediatric Research Day, East Lansing MI March 2019 Notes: Won Best Overall Poster Presentation.

Chasse, M.H., Johnson, B.K., Boguslawski, E.A., Sorensen, K.M., Beddows, I., Madaj, Z.B., Foxa, G.E., Rybski, K.J., Kitchen-Goosen, S.M., Williams, B.O., Triche Jr., T.J., Grohar, P.J.: Mithramycin evicts SWI/SNF from chromatin to induce epigenetic reprogramming in rhabdoid tumor. Peer Reviewed Poster Presentation Invited for an Oral Presentation at the 18th Annual State of Michigan Pediatric Research Day, East Lansing MI March 2019.

2018

Sorensen, K., Jess, J., Kitchen-Goosen, S.M., Flores, G.,Madaj, Z.B., Boguslawski, E.,Grohar, P.J. : Oxiliplatin and ATR inhibitors show strong synergy in Ewing sarcoma cells. Peer Reviewed Poster Presentation at the Annual Meeting of the American Association for Cancer Research, Chicago, IL April 2018.

Kitchen-Goosen, S.M., Bowman, M.J., Adams, M., Berger, P., Grohar, P.J. : The EWS-FLI1 transcriptome is characterized by marked heterogeneity across cell lines  Peer Reviewed Poster Presentation at the Annual Meeting of the American Association for Cancer Research, Chicago, IL April 2018.

Flores, G., Everett, J., Oswald, B.,Caplen, N., Helman, L.J., Madaj, Z.B., Grohar, P.J.: Suppression of EWS-FLI1 transcription using a combination therapy of mithramycin and cyclin dependent kinase 9 inhibition. Peer Reviewed Poster Presentation for Pediatric Cancer at the Annual Meeting of the American Association for Cancer Research, Chicago, IL April 2018.

Chasse, M.H., Boguslawski, El, Wernette, C.E., Kitchen-Goosen, S.M., Grohar, P.J.: Mithramycin amplifies the imbalance between the BAF and PRC2 complexes to drive apoptosis in rhabdoid tumor. Peer Reviewed Oral Presentation, Annual Meeting of the American Association for Cancer Research, Chicago, IL April 2018 Notes: AACR Margaret Foti Scholar-in-Training Award in Pediatric Cancer Research.

Invited Lectures

2019

Grohar PJ. "Development of a Pharmacodynamic Marker of EWS-FLI1 Activity to Aid in the Clinical Translation of Targeted Therapies in EWS", In Alex's Lemonade Stand Innovation Summit, Philadelphia, PA. Sept 2019.

Grohar PJ. "A bench-to-bedside approach targeting EWS-FLI1 for Ewing sarcoma", MD Anderson Cancer Center Pediatric Grand Rounds, Houston, TX. Jan 2019.

2018

Grohar PJ. "A bedside-to-bench approach targeting EWS-FLI1 for Ewing sarcoma" In Memorial Sloan Kettering Pediatric Oncology Grand Rounds, New York, New York. Sep, 2018.

Grohar PJ. "A bench-to-bedside approach targeting EWS-FLII for Ewing sarcoma" In Research Seminar, Emory University Division of Pediatric Hematology Oncology, Atlanta, GA. Aug, 2018.

Grohar PJ. "Development and translation of EWS-FLI1 targeted therapy for Ewing sarcoma" In Research Seminar, University of Michigan Division of Pediatric Hematology Oncology, Ann Arbor, MI. Jul, 2018.

Grohar PJ. "A bench-to-bedside approach to the therapeutic targeting of EWS-FLi1 for Ewing sarcoma" In Grand Rounds, Georgetown University Lombardi Cancer,  Washington, D.C. May, 2018.

Grohar PJ. "Therapeutic targeting of EWS-FLI1 for Ewing sarcoma" In Children's Oncology Group Spring Meeting; Combined Sarcoma Biology Session, St. Louis MO. Apr, 2018.

Grohar PJ. "A bench-to-bedside approach to the therapeutic targeting of EWS-FLII for Ewing sarcoma" In Children's Hospital of Philadelphia, Research Seminar,  Philadelphia, PA. Apr, 2018.

2017

Grohar PJ. "A bench to bedside approach targeting EWS-FLI1 for Ewing sarcoma" In University of Kansas Comprehensive Cancer Center Research Symposium,  Overland Park, Kansas. Dec, 2017.

Grohar PJ. "Development of targeted therapies for EWS-FLII and Ewing sarcoma" In Sarcoma Alliance for Research Through Collaboration Bi-annual Meeting,  Maui, HI. Nov, 2017.

Grohar PJ. "Translocation positive Ewing sarcoma: An opportunity for targeted therapy" In American Society for Clinical Oncology Annual Meeting, Chicago, IL. Jun, 2017.

Grohar PJ. "Molecular targeting of the EWS-FLI1 transcription factor for Ewing sarcoma" In University of Kentucky Cancer Center Seminar Series, Lexington, KY. Apr, 2017.

Grohar PJ. "Sustained suppression of EWS-FLI1 in Ewing sarcoma" In Children's Oncology Group Spring Meeting, St. Louis MO. Mar, 2017.

Awards and Honors

2018, Alex’s Lemonade Stand: Northwestern Mutual Innovative Grant Award
2017, St. Baldrick’s Scholar
2013-2015, Junior Faculty Development Program, Vanderbilt University School of Medicine
2011, Fellows Award for Research Excellence (FARE), National Institutes of Health
2010, Finalist, American Association for Cancer Research (AACR) Scholar in Training Award
2008-2010, Pediatric Oncology Branch Research Competition - 1st Place: Fellows Post Docs (Annually for three years), Johns Hopkins University/National Institutes of Health
2006-2011, Competitive National Institutes of Health Loan Repayment Program for General Research (5 renewals awarded)
2001-2003, Graduation with Distinction in Biomedical Research, Wayne State University
2001-2003, Aesculapians Medical Student Service Honor Society
1997, Phi Lambda Upsilon National Chemistry Honor Society

Editorial and Academic Positions

Editorial Positions

Ad Hoc Reviewer

2019, Drug Discovery and Molecular Pharmacology (DMP)
2017-2018, National Institutes of Health, Cancer and Molecular Pathobiology (CAMP)
2017-present, Cancer Cell
2017-present, Science
2015-present, St. Baldrick’s Foundation
2011-present, PLOS one
2011-present, Frontiers in Medicine
2011-present, Oncotarget
2011-present, Cancer Research
2011-present, BMC Cancer
2011-present, Frontiers in Pediatrics
2011-present, Clinical Cancer Research
2011-present, International Journal of Nanomedicine
2011-present, Journal of Clinical Investigation
2011-present, Leukemia
2011-present, Genes and Cancer
2011-present, Sarcoma
2011-present, Molecular Cancer Research

Academic and Institutional Committees

2017-present, Cancer Prevention Research Institute of Texas (CPRIT), Cancer Biology Panel, standing member
2015-present, Alex’s Lemonade Stand, Scientific Review Board
 

Leadership and Memberships

Memberships in Professional Organizations

2017-present, Children’s Oncology Group Therapeutic Task Force
 - 2019-present, Osteosarcoma
 - 2017-present, Ewing Sarcoma
2016-present, QuadW-Biospecimen Committee
2011-present, Connective Tissue Oncology Society
2011-present, Children’s Oncology Group
2009-present, American Association for Cancer Research

Leadership

2019-present, Vice-Chair for Biology, Bone Tumor Committee
2019-present, Chair, Ewing Sarcoma Biology Committee
2015-present, Children’s Oncology Group, Bone Tumor Steering Committee
2015-2019, Vice-Chair, Ewing Sarcoma Biology Committee
2018-present, Co-Chair, Combined Sarcoma Biology Committee