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Bobby Bowman, Ph.D.
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Assistant Professor of Cancer Biology
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Department: Cancer Biology
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Graduate Group Affiliations
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Contact information
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421 Curie Blvd
Philadelphia, PA 19104
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Philadelphia, PA 19104
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Education:
21 7 BA 2e (Molecular Cellular Biology Honors) c
2e Vanderbilt University, 2010.
21 8 PhD 33 (Cancer Biology (Mentor: Johanna Joyce)) c
42 Gerstner Sloan Kettering Graduate Program, 2016.
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Permanent link21 7 BA 2e (Molecular Cellular Biology Honors) c
2e Vanderbilt University, 2010.
21 8 PhD 33 (Cancer Biology (Mentor: Johanna Joyce)) c
42 Gerstner Sloan Kettering Graduate Program, 2016.
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303 We are interested in studying the evolution of cancer development from pre-malignancy through transformation. Hematologic malignancies are an ideal disease model to study classical questions in cancer biology, given sample access and extensive description of the normal hematopoietic differentiation cascade. Genetic studies in acute myeloid leukemia (AML) have revealed a hierarchical arrangement of mutations such that certain mutations are postulated to be acquired either early or late in disease progression. This stepwise acquisition of mutations results in a genetically heterogeneous collection of clones contributing to disease development. Through the progression from pre-malignancy to leukemic transformation, we study the following broad questions:
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53 1) What are the necessary steps for a mutant cell to transform to leukemia?
58 2) After transformation, how do leukemic cells affect normal non-mutated cells?
73 3) How can we revert or halt transformed cells early in disease development to prevent disease development?
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a1 We approach these questions through an intersection of genomic profiling of patient samples and synthetic biology approaches for modeling disease in mice
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19 Bowman Lab
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39f The major focus of the lab is on the receptor tyrosine kinase, FLT3, which is the most commonly mutated gene in AML and typically presents as a subclonal, late event. Mutations can manifest as internal tandem duplications (ITDs) in the juxtamembrane domain leading to constitutive kinase activation. Despite being mutated in only a subset of leukemic cells, FLT3 mutations are associated with poor prognosis. Tyrosine kinase inhibitors (TKIs e.g. gilteritinib) demonstrate substantive clinical efficacy, but invariably lead to relapse. It remains unclear when a given leukemia is dependent upon FLT3 mutations, and how a subclonal oncogene portends such poor prognosis yet has therapeutic utility. In a broader context, understanding the functional roles of clonal and subclonal mutations in AML initiation and maintenance has fundamental mechanistic and therapeutic implications. Current projects in the lab focus on:
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136 1: Oncogenic dependency in leukemic stem cells We will seek to understand how quiescent leukemic stem cells respond to therapy by juxtaposing chemical vs genetic inhibition. In the long term seek to understand how cooperating mutations influence the quantity and characteristics of this stem cell pool.
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1cc 2: Evaluating cell of origin in FLT3-driven acute myeloid leukemia. We hypothesize that different cooperating mutations influence the cell of origin of FLT3 driven disease. Our lab will approach this question using inducible mouse models and synthetic biology approaches for cell type specific control. In the long term, we seek to progress towards complete in vivo modeling through the development of novel cell type specific recombinase mouse lines.
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320 3 : Investigate interclonal interactions in leukemic progression. We hypothesize that this stepwise acquisition of mutations results in a genetically diverse ecosystem where clones interact either in supporting or suppressing other genetically distinct clones. Our group will investigate inter-clonal interactions and competition through the lens of FLT3 mutant AML, investigating several key questions including: Does the presence of a FLT3-mutant clone affect the fitness of antecedent clones? To investigate clonal heterogeneity and paracrine interactions we will integrate single cell genomic profiling in clinical isolates and mouse models of subclonal FLT3-mutations, mechanistically evaluate candidate paracrine factors ex vivo, and evaluate their role in disease progression in vivo.
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1c Lab Personnel
6c Lesley Moreno - Administrative Assistant Ljmoreno@upenn.edu
2b Nisarg Shah - Research Specialist D
2b Angela Youn - Research Specialist A
34 Michael Bowman PhD - Postdoctoral Researcher
3b Roopsha Bandopadhyay - PhD Student - Bioengineering
31 Anushka Gandhi - Undergraduate Researcher
32 Shreeya Gounder - Undergraduate Researcher
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Description of Research Expertise
28 Current Research8
303 We are interested in studying the evolution of cancer development from pre-malignancy through transformation. Hematologic malignancies are an ideal disease model to study classical questions in cancer biology, given sample access and extensive description of the normal hematopoietic differentiation cascade. Genetic studies in acute myeloid leukemia (AML) have revealed a hierarchical arrangement of mutations such that certain mutations are postulated to be acquired either early or late in disease progression. This stepwise acquisition of mutations results in a genetically heterogeneous collection of clones contributing to disease development. Through the progression from pre-malignancy to leukemic transformation, we study the following broad questions:
8
53 1) What are the necessary steps for a mutant cell to transform to leukemia?
58 2) After transformation, how do leukemic cells affect normal non-mutated cells?
73 3) How can we revert or halt transformed cells early in disease development to prevent disease development?
8
a1 We approach these questions through an intersection of genomic profiling of patient samples and synthetic biology approaches for modeling disease in mice
8
19 Bowman Lab
8
39f The major focus of the lab is on the receptor tyrosine kinase, FLT3, which is the most commonly mutated gene in AML and typically presents as a subclonal, late event. Mutations can manifest as internal tandem duplications (ITDs) in the juxtamembrane domain leading to constitutive kinase activation. Despite being mutated in only a subset of leukemic cells, FLT3 mutations are associated with poor prognosis. Tyrosine kinase inhibitors (TKIs e.g. gilteritinib) demonstrate substantive clinical efficacy, but invariably lead to relapse. It remains unclear when a given leukemia is dependent upon FLT3 mutations, and how a subclonal oncogene portends such poor prognosis yet has therapeutic utility. In a broader context, understanding the functional roles of clonal and subclonal mutations in AML initiation and maintenance has fundamental mechanistic and therapeutic implications. Current projects in the lab focus on:
8
136 1: Oncogenic dependency in leukemic stem cells We will seek to understand how quiescent leukemic stem cells respond to therapy by juxtaposing chemical vs genetic inhibition. In the long term seek to understand how cooperating mutations influence the quantity and characteristics of this stem cell pool.
9
1cc 2: Evaluating cell of origin in FLT3-driven acute myeloid leukemia. We hypothesize that different cooperating mutations influence the cell of origin of FLT3 driven disease. Our lab will approach this question using inducible mouse models and synthetic biology approaches for cell type specific control. In the long term, we seek to progress towards complete in vivo modeling through the development of novel cell type specific recombinase mouse lines.
8
320 3 : Investigate interclonal interactions in leukemic progression. We hypothesize that this stepwise acquisition of mutations results in a genetically diverse ecosystem where clones interact either in supporting or suppressing other genetically distinct clones. Our group will investigate inter-clonal interactions and competition through the lens of FLT3 mutant AML, investigating several key questions including: Does the presence of a FLT3-mutant clone affect the fitness of antecedent clones? To investigate clonal heterogeneity and paracrine interactions we will integrate single cell genomic profiling in clinical isolates and mouse models of subclonal FLT3-mutations, mechanistically evaluate candidate paracrine factors ex vivo, and evaluate their role in disease progression in vivo.
8
1c Lab Personnel
6c Lesley Moreno - Administrative Assistant Ljmoreno@upenn.edu
2b Nisarg Shah - Research Specialist D
2b Angela Youn - Research Specialist A
34 Michael Bowman PhD - Postdoctoral Researcher
3b Roopsha Bandopadhyay - PhD Student - Bioengineering
31 Anushka Gandhi - Undergraduate Researcher
32 Shreeya Gounder - Undergraduate Researcher
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51 Chow RD, Velu P, Deihimi S, Belman J, 27 Youn A, Shah N, Luger SM, Carroll MP, 33 Morrissette J, Bowman RL: Early drivers of 2d clonal hematopoiesis shape the evolutionary 27 trajectories of de novo acute myeloid 49 leukemia. Blood Adv. 9(8): 1888-1899, April 2025.
51 Sande CM, Chen S, Mitchell DV, Lin P, 22 Abraham DM, Cheng JM, Gebhard T, 2a Deolikar RJ, Freeman C, Zhou M, Kumar S, 1f Bowman M, Bowman RL, Zheng S, 2a Munkhbileg B, Chen Q, Stanley NL, Guo K, 2c Lapite A, Hausler R, Taylor DM, Corines J, 27 Morrissette JJ, Lieberman DB, Yang G, 2b Shestova O, Gill S, Zheng J, Smith-Simmer 27 K, Banaszak LG, Shoger KN, Reinig EF, 2c Peterson M, Nicholas P, Walne AJ, Dokal I, 2a Rosenheck JP, Oetjen KA, Link DC, Gelman 26 AE, Reilly CR, Dutta R, Lindsley RC, 25 Brundige KJ, Agarwal S, Bertuch AA, 29 Churpek JE, Tague LK, Johnson FB, Olson 2d TS, Babushok DV. : ATM-dependent DNA 2c damage response constrains cell growth and 29 drives clonal hematopoiesis in telomere 6b biology disorders. J Clin Invest 135(8), April 2025 Notes: doi: 10.1172/JCI181659.
54 Shah N, Chow R, Velu P, Luger S, Carroll 59 M, Morrissette J, Bowman M, Bowman RL: Evolutionary trajectories and single cell 29 methylation analysis of DNMT3A and TET2 55 mutant acute myeloid leukemia. American Association for Cancer Research: Clonal 2c Hematopoiesis| Feb 2025.
ba Cai X, Bowman RL, Trowbridge JT: Clonal hematopoiesis in the cancer setting. Nature Cancer 2025 Notes: In Press.
4d Bowman RL**, Dunbar AJ, Mishra T, 2b Xiao W, Waarts MR, Maestre IF, Eisman SE, 2c Cai L, Mowla S, Shah N, Youn A, Bennett L, 2a Fontenard S, Gounder S, Gandhi A, Bowman 2b M, O'Connor K, Zaroogian Z, Sánchez-Vela 2a P, Martinez Benitez AR, Werewski M, Park 2c Y, Csete IS, Krishnan A, Lee D, Boorady N, 2b Potts CR, Jenkins MT, Cai SF, Carroll MP, 24 Meyer SE, Miles LA, Ferrell PB Jr, 35 Trowbridge JJ, Levine RL.: In vivo models of 29 subclonal oncogenesis and dependency in 55 hematopoietic malignancy. Cancer Cell. 42(11): 1955-1969, Nov 2024 Notes: doi: 30 10.1016/j.ccell.2024.10.009.
4e Drucker M, Lee D, Zhang X, Kain B, 28 Bowman M, Nicolet D, Wang Z, Stone RM, 2a Mrózek K, Carroll AJ, Starczynowski DT, 2b Levine RL, Byrd JC, Eisfeld AK, Salomonis 55 N, Grimes HL, Bowman RL, Miles LA: Genotype-immunophenotype relationships in 22 NPM1-mutant AML clonal evolution 52 uncovered by single cell multiomic analysis. bioRxiv Nov 12 2024 Notes: doi: 2e 10.1101/2024.11.11.623033.
55 Nazaret A, Fan JL, Lavallée VP, Burdziak 29 C, Cornish AE, Kiseliovas V, Bowman RL, 2a Masilionis I, Chun J, Eisman SE, Wang J, 2e Hong J, Shi L, Levine RL, Mazutis L, Blei D, 34 Pe'er D, Azizi E.: Joint representation and 2c visualization of derailed cell states with 2c Decipher. bioRxiv Nov 2024 Notes: doi: 2e 10.1101/2023.11.11.566719.
4f Goda C, Kulkarni R, Bustos Y, Li W, 2d Rudich A, Balcioglu O, Chidester S, Urs AP, 2b Karunasiri M, Al-Marrawi Y, Korn E, Kanna 25 S, Garfinkle EAR, Shah N, Wooten A, 23 Mundy-Bosse B, Sehgal L, Zhang B, 29 Marcucci G, Mardis ER, Garzon R, Bowman 23 RL, Viny AD, Miles LA, Miller KE, 2f Dorrance AM.: Cellular taxonomy of the 28 preleukemic bone marrow niche of acute 64 myeloid leukemia. Leukemia Oct 2024 Notes: doi: 10.1038/s41375-024-02415-3.
51 Tiedje V, Vela PS, Yang JL, Untch BR, 2e Boucai L, Stonestrom AJ, Costa AB, Expósito 2c SF, Srivastava A, Kerpelev M, Greenberg J, 2c Wereski M, Kulick A, Chen K, Qin T, Im SY, 2b Krishnan A, Martinez Benitez AR, Pluvinet 2b R, Sahin M, Menghrajani K, Krishnamoorthy 2e GP, de Stanchina E, Zehir A, Satija R, Knauf 2c J, Bowman RL, Esteller M, Devlin S, Berger 57 MF, Koche RP, Fagin JA, Levine RL.: Targetable treatment resistance in thyroid 44 cancer with clonal hematopoiesis. bioRxiv Oct 2024 Notes: doi: 2e 10.1101/2024.10.10.617685.
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Selected Publications
52 Sakamoto T, Leca J, Zhang X, Meydan C, 27 Foox J, Ramachandran P, Hendrikse LD, 26 Zhou W, Berger T, Fortin J, Chan SM, 24 Chiang MF, Inoue S, Li WY, Chu MF, 24 Duncan GS, Wakeham A, Lemonnier F, 2a Tobin C, Mcwilliam R, Colonna I, Bontoux 25 C, Jafari SM, Bowman RL, Nicolay B, 29 Ronseaux S, Narayanaswamy R, Levine RL, 26 Melnick AM, Mason CE, Minden MD, Mak 32 TW.: Mutant IDH1 cooperates with NPM1c or 2e FLT3(ITD) to drive distinct myeloid diseases 30 and molecular outcomes. Proc Natl Acad Sci 51 U S A. 122(20), May 2025 Notes: doi: 10.1073/pnas.2415779122.51 Chow RD, Velu P, Deihimi S, Belman J, 27 Youn A, Shah N, Luger SM, Carroll MP, 33 Morrissette J, Bowman RL: Early drivers of 2d clonal hematopoiesis shape the evolutionary 27 trajectories of de novo acute myeloid 49 leukemia. Blood Adv. 9(8): 1888-1899, April 2025.
51 Sande CM, Chen S, Mitchell DV, Lin P, 22 Abraham DM, Cheng JM, Gebhard T, 2a Deolikar RJ, Freeman C, Zhou M, Kumar S, 1f Bowman M, Bowman RL, Zheng S, 2a Munkhbileg B, Chen Q, Stanley NL, Guo K, 2c Lapite A, Hausler R, Taylor DM, Corines J, 27 Morrissette JJ, Lieberman DB, Yang G, 2b Shestova O, Gill S, Zheng J, Smith-Simmer 27 K, Banaszak LG, Shoger KN, Reinig EF, 2c Peterson M, Nicholas P, Walne AJ, Dokal I, 2a Rosenheck JP, Oetjen KA, Link DC, Gelman 26 AE, Reilly CR, Dutta R, Lindsley RC, 25 Brundige KJ, Agarwal S, Bertuch AA, 29 Churpek JE, Tague LK, Johnson FB, Olson 2d TS, Babushok DV. : ATM-dependent DNA 2c damage response constrains cell growth and 29 drives clonal hematopoiesis in telomere 6b biology disorders. J Clin Invest 135(8), April 2025 Notes: doi: 10.1172/JCI181659.
54 Shah N, Chow R, Velu P, Luger S, Carroll 59 M, Morrissette J, Bowman M, Bowman RL: Evolutionary trajectories and single cell 29 methylation analysis of DNMT3A and TET2 55 mutant acute myeloid leukemia. American Association for Cancer Research: Clonal 2c Hematopoiesis| Feb 2025.
ba Cai X, Bowman RL, Trowbridge JT: Clonal hematopoiesis in the cancer setting. Nature Cancer 2025 Notes: In Press.
4d Bowman RL**, Dunbar AJ, Mishra T, 2b Xiao W, Waarts MR, Maestre IF, Eisman SE, 2c Cai L, Mowla S, Shah N, Youn A, Bennett L, 2a Fontenard S, Gounder S, Gandhi A, Bowman 2b M, O'Connor K, Zaroogian Z, Sánchez-Vela 2a P, Martinez Benitez AR, Werewski M, Park 2c Y, Csete IS, Krishnan A, Lee D, Boorady N, 2b Potts CR, Jenkins MT, Cai SF, Carroll MP, 24 Meyer SE, Miles LA, Ferrell PB Jr, 35 Trowbridge JJ, Levine RL.: In vivo models of 29 subclonal oncogenesis and dependency in 55 hematopoietic malignancy. Cancer Cell. 42(11): 1955-1969, Nov 2024 Notes: doi: 30 10.1016/j.ccell.2024.10.009.
4e Drucker M, Lee D, Zhang X, Kain B, 28 Bowman M, Nicolet D, Wang Z, Stone RM, 2a Mrózek K, Carroll AJ, Starczynowski DT, 2b Levine RL, Byrd JC, Eisfeld AK, Salomonis 55 N, Grimes HL, Bowman RL, Miles LA: Genotype-immunophenotype relationships in 22 NPM1-mutant AML clonal evolution 52 uncovered by single cell multiomic analysis. bioRxiv Nov 12 2024 Notes: doi: 2e 10.1101/2024.11.11.623033.
55 Nazaret A, Fan JL, Lavallée VP, Burdziak 29 C, Cornish AE, Kiseliovas V, Bowman RL, 2a Masilionis I, Chun J, Eisman SE, Wang J, 2e Hong J, Shi L, Levine RL, Mazutis L, Blei D, 34 Pe'er D, Azizi E.: Joint representation and 2c visualization of derailed cell states with 2c Decipher. bioRxiv Nov 2024 Notes: doi: 2e 10.1101/2023.11.11.566719.
4f Goda C, Kulkarni R, Bustos Y, Li W, 2d Rudich A, Balcioglu O, Chidester S, Urs AP, 2b Karunasiri M, Al-Marrawi Y, Korn E, Kanna 25 S, Garfinkle EAR, Shah N, Wooten A, 23 Mundy-Bosse B, Sehgal L, Zhang B, 29 Marcucci G, Mardis ER, Garzon R, Bowman 23 RL, Viny AD, Miles LA, Miller KE, 2f Dorrance AM.: Cellular taxonomy of the 28 preleukemic bone marrow niche of acute 64 myeloid leukemia. Leukemia Oct 2024 Notes: doi: 10.1038/s41375-024-02415-3.
51 Tiedje V, Vela PS, Yang JL, Untch BR, 2e Boucai L, Stonestrom AJ, Costa AB, Expósito 2c SF, Srivastava A, Kerpelev M, Greenberg J, 2c Wereski M, Kulick A, Chen K, Qin T, Im SY, 2b Krishnan A, Martinez Benitez AR, Pluvinet 2b R, Sahin M, Menghrajani K, Krishnamoorthy 2e GP, de Stanchina E, Zehir A, Satija R, Knauf 2c J, Bowman RL, Esteller M, Devlin S, Berger 57 MF, Koche RP, Fagin JA, Levine RL.: Targetable treatment resistance in thyroid 44 cancer with clonal hematopoiesis. bioRxiv Oct 2024 Notes: doi: 2e 10.1101/2024.10.10.617685.
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