Faculty

Adam J Wolpaw, MD, PhD

Assistant Professor of Pediatrics (Oncology)

Department: Pediatrics

Graduate Group Affiliations

Cell and Molecular Biology

Contact information

Children’s Hospital of Philadelphia
Division of Oncology
3500 Civic Center Blvd
Philadelphia, PA 19104

Office: 917-566-0256

Email:
wolpawa@chop.edu

Publications

Search PubMed for articles

Education:
Sc.B. (Chemistry. Magna Cum Laude )
Brown University, 2003.
M.Phil. (Pharmacology)
Cambridge University, 2004.
PhD (Chemical Biology, Integrated Program in Cellular, Molecular, and Biomedical Studies)
Columbia University College of Physicians and Surgeons, 2011.
MD (Medicine)
Columbia University College of Physicians and Surgeons, 2012.

Links
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Permanent link

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Description of Clinical Expertise

I have particular expertise in the care of children with solid tumors.

Description of Research Expertise

Research Interests:
My laboratory is focused on understanding the impact of tumor heterogeneity on inflammatory signaling and immunotherapy response in pediatric solid tumors with a goal of improving therapy.

Keywords:
Tumor heterogeneity
Lineage heterogeneity
Immunotherapy
Pattern recognition receptors
cGAS-STING signaling
Neuroblastoma
Pediatric cancer

Research detail:
Our work has centered on the childhood tumor, neuroblastoma. Neuroblastoma cells can exist in one of two epigenetic or lineage states, an "adrenergic" state that comprises the majority of the bulk tumor and tends to be responsive to chemotherapy, and a "mesenchymal" state that is a more minor subpopulation and more resistant to chemotherapy. We found that the mesenchymal cells are much more sensitive to inflammatory stimuli and have a higher basal level of inflammation than the adrenergic cells, revealing a potential immune vulnerability of this important drug-resistant state. We are now investigating how to model these states and how to exploit that vulnerability to enhance therapy for neuroblastoma patients. We are also interested in applying similar principles to other pediatric solid tumors.

Potential Rotation Projects:
1) Investigating the identity and role of endogenous cytosolic DNA in neuroblastoma evolution and immunotherapeutic responses.

2) Genome-wide CRISPR screening to identify lineage state-dependent and state-independent mechanisms of regulation of immunotherapeutic surface targets.

3) Impact of lineage heterogeneity on CAR T cell efficacy and dual antigen targeting strategies to overcome resistance (joint project with laboratory of Kris Bosse).

Laboratory Personnel:
Piotr Jung (Post-doctoral Fellow)
Matthew Shapiro (Senior Technician)
Alaa Narch (Technician)
Kevin Bayingana (Technician)
Rebecca DeJesus (Mouse Technician)
Bessy Joseph (Administrative support)

Selected Publications

Wolpaw AJ, Grossmann LD, Dong MM, Dessau JL, Brafford PA, Volgina D, Rodriguez-Garcia A, Uzun Y, Powell Jr, JD, Tan K, Hogarty MD, Maris JM, Dang CV. : “Epigenetic state determines inflammatory sensing in neuroblastoma.” Proc Natl Acad Sci U S A. 119(6), Feb 2022.

McNerney, KO, Karageorgos S, Ferry G, Wolpaw AJ, Burudpakdee C, Khurana P, Vemu R, Vu A, Hogarty MD, Bassiri H: TH-MYCN tumors, but not tumor-derived cell lines, are adrenergic lineage, GD2+, and responsive to anti-GD2 antibody therapy. OncoImmunology 11(1): 2075204, May 2022.

Wolpaw AJ, Bayless R, Buchel G, Dang CV, Eilers M, Gustafson WC, Hansen GH, Jura N, Knapp S, Lemmon MA, Levens D, Maris JM, Marmorstein R, Metallo SJ, Park JR, Penn LZ, Rape M, Rouseel MF, Shokat KM, Tansey WP, Verba KA, Vos SM, Weiss WA, Wolf E, Mosse YP: Drugging the 'undruggable' MYCN oncogenic transcription factor: Overcoming previous obstacles to impact childhood cancers. Cancer Res 81(7): 1627-1632, Apr 2021.

Wolpaw, A. J., Dang, C. V.: Exploiting Metabolic Vulnerabilities of Cancer with Precision and Accuracy. Trends Cell Biol 28(3): 201-212, Mar 2018.

Wolpaw, A. J., Dang, C. V.: MYC-induced metabolic stress and tumorigenesis. Biochim Biophys Acta Rev Cancer 1870(1): 43-50, Aug 2018.

Shimada K, Skouta R, Kaplan A, Yang WS, Hayano M, Dixon SJ, Brown LM, Valenzuela CA, Wolpaw AJ, Stockwell BR. : “Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis.” Nat Chem Biol 12(7): 497-503, Jul 2016.

Wolpaw AJ, Stockwell BR: “Multidimensional profiling methodologies in the investigation of small-molecule-induced cell death.” Methods in Enzymology Page: 265-302, 2014.

Wolpaw AJ, Shimada K, Skouta R, Welsch ME, Akavia UR, Pe’er D, Shaik F, Bulinski JC, Stockwell BR.: “Modulatory profiling identifies mechanisms of small molecule-induced cell death.” Proc Natl Acad Sci 108(39): E771-780 Sep 2011.

Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS, Fridman DJ, WOLPAW AJ, Smukste I, Peltier JM, Boniface JJ, Smith R, Lessnick SL, Sahasrabudhe S, Stockwell BR. : “RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels.” Nature 447: 864-868, Jun 2007.

Wolpaw, AJ, Aizer AA, Zimmt MB.: “Synthesis of self-orienting triptycene adsorbates for STM investigations.” Tetrahedron Letters 44(41): 7613-7615 Oct 2003.