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richmans [at] email.chop.edu
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Room 4020

3501 Civic Center Blvd
Philadelphia, PA 19104
United States

Research Topics
Sarah A. Richman, MD, PhD
Sarah A. Richman Headshot
Attending Physician

Dr. Richman's research focuses on chimeric antigen receptor (CAR) T cells targeting solid tumors with the goal of translating these findings to this unmet clinical need.

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Bio

Dr. Richman has a longstanding interest in using T cells to target cancer. For her PhD research in the lab of Dr. Davis Kranz at the University of Illinois, she focused on engineering the alpha-beta T cell receptor (TCR) for potential therapeutic applications. There she developed a novel method for selecting high-affinity variants of antigen-specific TCRs in order to enhance recognition of tumor antigens. She also investigated TCR regions most critical for domain stability, modification of which permits expression as single-chain TCRs amenable to genetic redirection of T cells using a single polypeptide.

After completing her MD/PhD program and pediatrics residency at Columbia University Medical Center, Dr. Richman completed the Hematology-Oncology fellowship at CHOP in 2016 and is currently an instructor in the Division of Oncology. Since the second year of her fellowship, she has worked on CAR T cells in Michael Milone's lab at the University of Pennsylvania.

In Dr. Milone's lab she has focused on a preclinical model of anti-GD2 CAR T cell therapy for neuroblastoma, and her studies described severe neurotoxicity associated with a more potent version of the CAR. Informed by those findings, along with a similar pattern in other tumor models, she is focusing her current efforts in the lab on understanding how to mitigate off-tumor toxicity while maintaining high anti-tumor potency.

Education and Training

AB, Princeton University (Molecular Biology), 2001

PhD, University of Illinois at Urbana-Champaign (Biochemistry), 2007

MD, University of Illinois at Urbana-Champaign, 2010

Fellowship, Children's Hospital of Philadelphia (Pediatric Hematology/Oncology), 2016

Titles and Academic Titles

Attending Physician

Instructor of Pediatrics

Publication Highlights

Richman SA, Nunez-Cruz S, Moghimi B, Li LZ, Gershenson ZT, Mourelatos Z, Barrett DM, Grupp SA, Milone MC. High-affinity GD2-specific CAR T cells induce fatal encephalitis in a preclinical neuroblastoma model. Cancer Immunol Res. 2017 Nov; pii: canimm.0211.2017. doi: 10.1158/2326-6066.CIR-17-0211. PMID: 29180536
Schmitt TM, Aggen DH, Stromnes IM, Dossett ML, Richman SA, Kranz DM, Greenberg PD. Enhanced-affinity murine T-cell receptors for tumor/self-antigens can be safe in gene therapy despite surpassing the threshold for thymic selection. Blood. 2013 Jul; 122(3):348-56. PMID: 23673862
Aggen DH, Chervin AS, Schmitt TM, Engels B, Stone JD, Richman SA, Piepenbrink KH, Baker BM, Greenberg PD, Schreiber H, and Kranz DM. Single-chain VaVb T cell receptors function without mispairing with endogenous TCR chains. Gene Ther. 2012 Apr; 19(4):365-74. PMID: 21753797
Richman SA, Weber KS, Buonpane RA, Donermeyer DL, Dossett ML, Allen PM, Greenberg PD, and Kranz DM. Structural features of T cell receptor variable regions that enhance domain stability and enable expression as single-chain VaVb fragments. Mol Immunol. 2009 Feb; 46(5): 902-916. PMID: 18962897
Richman SA, Healan SJ, Weber KS, Donermeyer DL, Dossett ML, Greenberg PD, Allen PM, Kranz DM. Development of a novel strategy for engineering high-affinity proteins by yeast display. Protein Eng Des, Sel. 2006 Jun; 19(6): 255-264. PMID: 16549400
Richman SA, Nunez-Cruz S, Moghimi B, Li LZ, Gershenson ZT, Mourelatos Z, Barrett DM, Grupp SA, Milone MC. High-affinity GD2-specific CAR T cells induce fatal encephalitis in a preclinical neuroblastoma model. Cancer Immunol Res. 2017 Nov; pii: canimm.0211.2017. doi: 10.1158/2326-6066.CIR-17-0211. PMID: 29180536
Schmitt TM, Aggen DH, Stromnes IM, Dossett ML, Richman SA, Kranz DM, Greenberg PD. Enhanced-affinity murine T-cell receptors for tumor/self-antigens can be safe in gene therapy despite surpassing the threshold for thymic selection. Blood. 2013 Jul; 122(3):348-56. PMID: 23673862
Aggen DH, Chervin AS, Schmitt TM, Engels B, Stone JD, Richman SA, Piepenbrink KH, Baker BM, Greenberg PD, Schreiber H, and Kranz DM. Single-chain VaVb T cell receptors function without mispairing with endogenous TCR chains. Gene Ther. 2012 Apr; 19(4):365-74. PMID: 21753797
Richman SA, Weber KS, Buonpane RA, Donermeyer DL, Dossett ML, Allen PM, Greenberg PD, and Kranz DM. Structural features of T cell receptor variable regions that enhance domain stability and enable expression as single-chain VaVb fragments. Mol Immunol. 2009 Feb; 46(5): 902-916. PMID: 18962897
Richman SA, Healan SJ, Weber KS, Donermeyer DL, Dossett ML, Greenberg PD, Allen PM, Kranz DM. Development of a novel strategy for engineering high-affinity proteins by yeast display. Protein Eng Des, Sel. 2006 Jun; 19(6): 255-264. PMID: 16549400

Active Grants/Contracts

Addressing toxicity in CAR-T therapy for solid tumors. St. Baldrick's Foundation, July 2017-June 2020. Role: PI