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Kristopher R. Bosse, MD
Assistant Professor of Pediatrics
The cure rate for children with neuroblastoma is unacceptable, making it imperative that new therapies are developed. Dr. Bosse's laboratory is focused on discovering and developing new neuroblastoma cell surface immunotherapeutic targets. Along with his colleagues, Dr. Bosse's aim is to capitalize on the robust differential expression of these molecules with immune-based therapies and also define their mechanisms of overexpression and roles in tumorigenesis.
Bio
Despite the use of intensive multimodal therapy for neuroblastoma, approximately one-half of children still die from this disease. Dr. Bosse's laboratory focuses on the development of new immune-based therapies for this embryonal malignancy of the developing nervous system. Through these studies, Dr. Bosse and his colleagues hope to both improve their understanding of the critical biologic mechanisms driving neuroblastoma tumorigenesis and to translate new transformative immunotherapeutics to the clinic.
To this end, Dr. Bosse and his colleagues have discovered that the lineage-restricted oncoprotein, glypican-2 (GPC2), is robustly and selectively expressed on the surface of neuroblastomas and that this molecule is essential to neuroblastoma tumorigenesis. They are now focused on defining the biology of neuroblastoma’s dependence on GPC2 and developing immunotherapeutic approaches targeting GPC2, including antibody-drug conjugates and chimeric antigen receptor (CAR) T cells. Using their immunotherapeutic target discovery algorithm and validation platform, they are also developing additional differentially expressed neuroblastoma cell surface molecules for immune-based therapies. This work is done as part of the St. Baldricks-Stand Up To Cancer Immunogenomics Team.
An additional project in Dr. Bosse's laboratory is focused on the serial sequencing of circulating tumor (ctDNA) from neuroblastoma patients to define tumor heterogeneity and clonal evolution while children are receiving both conventional chemoradiotherapies and also more targeted therapeutics. Dr. Bosse anticipates these efforts may both help define a role for ctDNA profiling in the clinical care of children with neuroblastoma and other pediatric solid tumors and also identify novel mutated driver oncogenes that warrant additional functional validation.
Finally, Dr. Bosse's laboratory is also interested in defining the functional implications of neuroblastoma-associated germline genetic variation, with a particular interest in describing the role of common and rare genetic variation in the regulation of BARD1 gene expression and how these alterations collectively contribute to neuroblastoma predisposition.
Education and Training
BA, Bowdoin College (Biochemistry), 2002
MD, University of Pennsylvania, 2010
Fellowship, Children's Hospital of Philadelphia (Hematology/Oncology), 2016
Titles and Academic Titles
Assistant Professor of Pediatrics
Attending Physician
Professional Awards
AACR-Aflac Scholar-in-Training Award, 2015, 2017, 2018
Damon Runyon Physician-Scientist Training Award, 2016
The EVAN Foundation Neuroblastoma Research Scholar, 2017
William Guy Forbeck Research Foundation Scholar Award, 2018
Publication Highlights
Pubmed:
Bosse KR, Raman P, Zhu Z, Lane M, Martinez D, Heitzeneder S, Rathi KS, Kendsersky NK, Randall M, Donovan L, Morrissy S, Sussman RT, Zhelev DV, Feng Y, Wang Y, Hwang J, Lopez G, Harenza JL, Wei JS, Pawel B, Bhatti T, Santi M, Ganguly A, Khan J, Marra MA, Taylor MD, Dimitrov DS, Mackall CL, Maris JM. Identification of GPC2 as an oncoprotein and candidate immunotherapeutic target in high-risk neuroblastoma. Cancer Cell. 2017 Sep; 32(3):295-309.e12. PMID: 28898695
Bosse KR, Maris JM. Advances in the translational genomics of neuroblastoma: From improving risk stratification and revealing novel biology to identifying actionable genomic alterations. Cancer. 2016 Jan; 122(1):20-33. doi: 10.1002/cncr.29706. PMID: 26539795
Bosse KR, Diskin SJ, Cole KA, Wood AC, Schnepp RW, Norris G, Jagannathan J, Laquaglia M, Winter C, Diamond M, Hou C, Attiyeh EF, Mosse YP, Dizin E, Zhang Y, Asgharzadeh S, Seeger RC, Capasso M, Pawel B, Devoto M, Hakonarson H, Rappaport ER, Irminger-Finger I, Maris JM. Common variation at BARD1 results in the expression of an oncogenic isoform that influences neuroblastoma susceptibility and oncogenicity. Cancer Res. 2012 Apr; 72(8):2068-78. doi: 10.1158/0008-5472. PMID: 22350409
Wang K, Diskin SJ, Zhang H, Attiyeh EF, Winter C, Hou C, Schnepp RW, Diamond M, Bosse K, Mayes PA, Glessner J, Kim C, Frackelton E, Garris M, Wang Q, Glaberson W, Chiavacci R, Nguyen L, Jagannathan J, Saeki N, Sasaki H, Grant S, Iolascon A, Mosse YP, Cole KA, Li H, Devoto M, McGrady PW, London WB, Capasso M, Rahman N, Hakonarson H, Maris JM. Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature. 2011 Jan; 469 (7329): 216-20. PMID: 21124317
Diskin SJ, Hou C, Glessner JT, Attiyeh EF, Laudenslager M, Bosse K, Cole K, Mosse YP, Wood A, Lynch JE, Pecor K, Diamond M, Winter C, Wang K, Kim C, Geiger EA, McGrady PW, Blakemore A, London WB, Shaikh TH, Bradfield J, Grant S, Li H, Devoto M, Rappaport ER, Hakonarson H, Maris JM. Copy number variation at 1q21.1 associated with neuroblastoma. Nature. 2009 Jun; 459 (7249): 987-91. PMID: 19536264