1e
19
1
49
2
2
18
1b
1d
18
34
51
1d
2 29
1d
25
Adam J Wolpaw, MD, PhD
88
51
Assistant Professor of Pediatrics (Oncology)
28
86
3
61
Attending Physician, Division of Oncology, Children's Hospital of Philadelphia
11
Department: Pediatrics
4
1
23
1f
Graduate Group Affiliations
8
a
b
1d
46
Contact information
53
4
3
3
1d
53
Children’s Hospital of Philadelphia
1c Division of Oncology
39 3500 Civic Center Blvd
Philadelphia, PA 19104
26
1c Division of Oncology
39 3500 Civic Center Blvd
Philadelphia, PA 19104
2e
Office: 917-566-0256
3f Lab: 215-590-9351
18
81
3f Lab: 215-590-9351
18
Email:
wolpawa@chop.edu
12
wolpawa@chop.edu
18
Publications
23 a
3
2
29
23 a
Links
b5 Search PubMed for articles
d
4
b
1f
b5 Search PubMed for articles
d
13
Education:
21 a Sc.B. 16 (Chemistry) c
29 Brown University, 2003.
21 c M.Phil. 19 (Pharmacology) c
2d Cambridge University, 2004.
21 8 PhD 60 (Chemical Biology, Integrated Program in Cellular, Molecular, and Biomedical Studies) c
4f Columbia University College of Physicians and Surgeons, 2011.
21 7 MD c
4f Columbia University College of Physicians and Surgeons, 2012.
c
3
3
3
3
8d
Permanent link21 a Sc.B. 16 (Chemistry) c
29 Brown University, 2003.
21 c M.Phil. 19 (Pharmacology) c
2d Cambridge University, 2004.
21 8 PhD 60 (Chemical Biology, Integrated Program in Cellular, Molecular, and Biomedical Studies) c
4f Columbia University College of Physicians and Surgeons, 2011.
21 7 MD c
4f Columbia University College of Physicians and Surgeons, 2012.
c
2 29
21
1e
1d
24
5e
71
be My laboratory is focused on understanding the impact of tumor heterogeneity on inflammatory signaling and therapy response in pediatric solid tumors with a goal of improving therapy.
8
11 Keywords:
1b Tumor heterogeneity
1d Lineage heterogeneity
15 Immunotherapy
25 Pattern recognition receptors
1c cGAS-STING signaling
15 Neuroblastoma
18 Pediatric cancer
8
18 Research detail:
32e 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.
8
24 Potential Rotation Projects:
86 1) Investigating the identity and role of endogenous cytosolic DNA in neuroblastoma evolution and immunotherapeutic responses.
8
a5 2) Using immunocompetent murine models to identify lineage-state specific impacts on the identity and geometry of immune cells in the tumor microenvironment.
8
a6 3) Investigating and enhancing the bystander effect (killing of antigen-negative tumor cells) after immunotherapy, antibody mediated and CAR T cell-mediated.
8
1d Laboratory Personnel:
29 Piotr Jung (Post-doctoral Fellow)
2f Sridhar Veluvolu (Post-doctoral Fellow)
2b Matthew Shapiro (Senior Technician)
1f Alaa Narch (Technician)
26 Cara Toland (Mouse Technician)
29 Phoebe Calkins (Graduate Student)
29 Christina Hong (Graduate Student)
28 Angelle Brown (PennPREP Student)
28 Pamela Mishra (Bioinformatician)
2c Bessy Joseph (Administrative support)
e 29
27
Description of Clinical Expertise
56 I have particular expertise in the care of children with solid tumors.71
Description of Research Expertise
24 Research Interests:be My laboratory is focused on understanding the impact of tumor heterogeneity on inflammatory signaling and therapy response in pediatric solid tumors with a goal of improving therapy.
8
11 Keywords:
1b Tumor heterogeneity
1d Lineage heterogeneity
15 Immunotherapy
25 Pattern recognition receptors
1c cGAS-STING signaling
15 Neuroblastoma
18 Pediatric cancer
8
18 Research detail:
32e 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.
8
24 Potential Rotation Projects:
86 1) Investigating the identity and role of endogenous cytosolic DNA in neuroblastoma evolution and immunotherapeutic responses.
8
a5 2) Using immunocompetent murine models to identify lineage-state specific impacts on the identity and geometry of immune cells in the tumor microenvironment.
8
a6 3) Investigating and enhancing the bystander effect (killing of antigen-negative tumor cells) after immunotherapy, antibody mediated and CAR T cell-mediated.
8
1d Laboratory Personnel:
29 Piotr Jung (Post-doctoral Fellow)
2f Sridhar Veluvolu (Post-doctoral Fellow)
2b Matthew Shapiro (Senior Technician)
1f Alaa Narch (Technician)
26 Cara Toland (Mouse Technician)
29 Phoebe Calkins (Graduate Student)
29 Christina Hong (Graduate Student)
28 Angelle Brown (PennPREP Student)
28 Pamela Mishra (Bioinformatician)
2c Bessy Joseph (Administrative support)
e 29
23
15e 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.
1eb 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.
db Wolpaw, A. J., Dang, C. V.: Exploiting Metabolic Vulnerabilities of Cancer with Precision and Accuracy. Trends Cell Biol 28(3): 201-212, Mar 2018.
ce Wolpaw, A. J., Dang, C. V.: MYC-induced metabolic stress and tumorigenesis. Biochim Biophys Acta Rev Cancer 1870(1): 43-50, Aug 2018.
139 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.
f2 Wolpaw AJ, Stockwell BR: Multidimensional profiling methodologies in the investigation of small-molecule-induced cell death. Methods in Enzymology 545(1): 265-302, 2014.
135 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.
174 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(1): 864-868, Jun 2007.
a3 Wolpaw, AJ, Aizer AA, Zimmt MB.: “Synthesis of self-orienting triptycene adsorbates for STM investigations.” 49 Tetrahedron Letters 44(41): 7613-7615, Oct 2003.
2c
7
1d
1f
Selected Publications
163 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): e2102358119, Feb 2022.15e 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.
1eb 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.
db Wolpaw, A. J., Dang, C. V.: Exploiting Metabolic Vulnerabilities of Cancer with Precision and Accuracy. Trends Cell Biol 28(3): 201-212, Mar 2018.
ce Wolpaw, A. J., Dang, C. V.: MYC-induced metabolic stress and tumorigenesis. Biochim Biophys Acta Rev Cancer 1870(1): 43-50, Aug 2018.
139 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.
f2 Wolpaw AJ, Stockwell BR: Multidimensional profiling methodologies in the investigation of small-molecule-induced cell death. Methods in Enzymology 545(1): 265-302, 2014.
135 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.
174 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(1): 864-868, Jun 2007.
a3 Wolpaw, AJ, Aizer AA, Zimmt MB.: “Synthesis of self-orienting triptycene adsorbates for STM investigations.” 49 Tetrahedron Letters 44(41): 7613-7615, Oct 2003.
2c