Hematopoietic stem and progenitor cells (HSPCs) are one of the most widely utilized stem cell populations in the clinic today. Defects in HSPCs result in numerous hematologic diseases such as myelodysplastic syndromes (MDS). We explore how hematopoietic stem and progenitor cells (HSPC) form during development, how these cells function to maintain healthy hematopoiesis lifelong, and how dysfunction in them leads to hematologic malignancies. 

Our studies combine the advantages of zebrafish and human cells to explore the development and genetic regulation of HSC biology. Zebrafish offer powerful genetic pliability, easily accessible in vivo imaging, numerous transplantation assays, and screening capabilities. Human cells allow us to decipher the conservation of our novel zebrafish findings to relevant human diseases and treatments. Through these studies, we anticipate identifying factors that are critical in the HSC formation and function, which can be used to inform therapeutic strategies to improve HSC function as well as HSC derivation from pluripotent stem cells.

Projects in the lab cover three main themes: 

i) Defining regulators critical for de novo production of hematopoietic stem cells (HSCs) and HSC-independent progenitors during embryogenesis 

ii) Deciphering how mutations found in human myelodysplastic syndromes (MDS) alter stem cell traits and influence differentiation choices

iii) Understanding how RNA and DNA binding proteins that are mutated in MDS affect R-loop structures in the nucleus

1. Makishima H, Bowman TV, Godley, LA. DDX41-associated susceptibility to myeloid neoplasms. Blood, 2023; blood.2022017715. doi: 10.1182/blood.2022017715. PMID: 36455200.

2. Fraint E, Lv P, Liu F, Bowman TV, and Tamplin OJ. Hematopoietic Stem and Progenitor Cell Identification and Transplantation in Zebrafish. Methods Mol Biol. 2023;2567:233-249. doi: 10.1007/978-1-0716-2679-5_15. PMID: 36255705.

3. Potts KS*, Cameron RC*, Barajas JM, Wallace L, Cervantes AL, Gupta V, Ghazale N, Pradhan K, McKinstry M, Bai X, Choudhary G, Shastri A, Verma A, Obeng E#, and Bowman TV#. Selective targeting of splicing factor mutant HSPCs via STAT3 inhibition. Cell Reports, 2022; 41(11):111825. doi: 10.1016/j.celrep.2022.111825. PMID: 36516770. PMCID: PMC9994853

4. Weinreb JT and Bowman TV. Clinical and mechanistic insights into the roles of DDX41 in haematological malignancies. FEBS Lett, 2022; 596(21):2736-2745. doi: 10.1002/1873-3468.14487. PMID: 36036093. PMCID: PMC9669125 

5. Choudhary GS, Pellagatti A, Agianian B, Smith MA, Bhagat TD, Gordon-Mitchell S, Sahu S, Pandey S, Shah N, Aluri S, Aggarwal R, Aminov S, Schwartz L, Steeples V, Booher RN, Ramachandra M, Samson M, Carbajal M, Pradhan K, Bowman TV, Pillai MM, Will B, Wickrema A, Shastri A, Bradley RK, Martell RE, Steidl UG, Gavathiotis E, Boultwood J, Starczynowski DT, Verma A. Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations. eLife, 2022; 30(11): e78136. doi: 10.7554/eLife.78136. PMID: 36040792. PMCID: PMC9427103

6. Weinreb JT, Gupta V, Sharvit E, Weil R, and Bowman TV#. Ddx41 inhibition of DNA damage signaling permits erythroid progenitor expansion in zebrafish. Haematologica, 2022; 107(3):664-654 doi:10.3324/haematol.2020.257246. PMID: 33763998. PMCID: PMC8883538

7. Ulloa BA, Habbsa S, Potts KP, Lewis A, McKinstry M, Payne SG, Flores J, Nizhnik A, Feliz Norberto M, Mosimann C, and Bowman TV#. Definitive Hematopoietic Stem Cells Minimally Contribute to Embryonic Hematopoiesis. Cell Reports, 2021; 36(11): 109703. doi: 10.1016/j.celrep.2021.109703.PMID:34525360. 

8. Bowman TV and Trompouki E. Sensing Stemness. Current Stem Cell Reports, 2021; doi: 10.1007/s40778-021-00201-w. PMID: 34868827. PMCID: PMC8639566

9. Weinreb JT, Ghazale N, Pradhan K, Gupta V, Potts KS, Tricomi B, Daniels NJ, Padgett RA, De Oliveira S, Verma AK, and Bowman TV#. Excessive R-loops Trigger an Inflammatory Cascade Leading to Aberrant HSPC Expansion. Developmental Cell, 2021; 56(5):627-640 e5. PMID: 33651979. 

10. Fraint E*, Ulloa BA*, Feliz Norberto M, Potts KS#, and Bowman TV#. Advances in Pre-clinical Hematopoietic Stem Cell Models and Possible Implications for Improving Therapeutic Transplantation. Stem Cells Translational Medicine, 2021; 10(3):337-345. PMCID: PMC7900582. 

11. Choudhuri A*, Trompouki E*, Abraham BJ, Colli LM, Kock KH, Mallard W, Yang ML, Vinjamur DS, Ghamari A, Sporrij A, Hoi K, Hummel B, Boatman S, Chan V, Tseng S. Nandakumar SK, Yang S, Lichtig A, Superdock M, Grimes SN, Bowman TV, Zhou Y, Takahashi S, Joehanes R, Cantor AB, Bauer DE, Ganesh SK, Rinn J, Alpert PS, Bulyk ML, Chanock SJ, Young RA, Zon LI. Common variants in signaling transcription-factor-binding Sites Drive phenotype variability in red blood cell traits. Nature Genetics, 2020; 52(12):1333-1345. PMCID: PMC7876911. 

12. Fraint E, Feliz Norberto M, and Bowman TV#. A Novel Conditioning-Free Hematopoietic Stem Cell Transplantation Model in Zebrafish. Blood Advances, 2020; 4(24):6189-98. PMCID: PMC7756993. 

13. Lefkopoulos S, Polyzou A, Derecka M, Bergo V, Cauchy P, Clapes T, Jerez Longres C, Onishi-Seebacher M, Yin N, Martagon N, Potts KS, Klaeyle L, Liu F, Bowman TV, Jenuwein T, Mione M, and Trompouki E. Repetitive elements induce a RIG-I-like receptor-mediated inflammation to regulate HSPC emergence Immunity, 2020; 53(5): 934-51, PMID:33159854 . 

14. Bowman TV. Improving AML Classification using Splicing Signatures. Clinical Cancer Research, 2020; PMID: 32317289.

15. Bowman TV and Query CC. Are all splicing mutations the same? Blood, 2020; 135(13): 978-9. PMID:32219349.

16. De La Garza A, Cameron RC, Gupta V, Fraint E, Nik S, and Bowman TV. The Splicing Factor Sf3b1 Regulates Erythroid Maturation and Proliferation via TGFβ signaling. Blood Advances, 2019; 3(14):2093-3104. PMCID: PMC6650725.

17. Nik S and Bowman TV. Splicing Factors in Neurodegeneration. WIREs RNA,2019; 10(4):e1532. 

18. Sorrells S*, Nik S*, Casey M, Cameron RC, Truong H, Toruno C, Gulfo M, Lowe A, Jette C, Stewart RA#, Bowman TV#. Spliceosomal components protect embryonic neurons from R-loop-mediated DNA damage and apoptosis. Disease Models and Mechanisms, 2018; 11(2): dmm031583. PMCID: PMC5894942. *Equal contribution. #Co-Corresponding authors.  

19. Potts K and Bowman TV. Modeling Myeloid Malignancies Using Zebrafish. Frontier Oncology, 2017; 7(297):1-13.

20. Habbsa S*, McKinstry M*, and Bowman TV. "Sea"-ing is Believing: In Vivo Imaging of Hematopoietic Stem Cells and Cancer Using Zebrafish. Current Stem Cell Reports, 2017

21. Nik S*, Weinreb J*, and Bowman TV. Developmental HSC Microenvironments: Lessons from Zebrafish. Stem Cell Microenvironments and Beyond, Adv. Exp. Med Biol, 2017; 1041.

22. Trompouki E, Flores-Figueroa E, Lucas D, and Bowman TV. From the Bedside to the Bench: New Discoveries on Blood Cell Fate and Function. Experimental Hematology, 2017; 47: 24-30.

23. De La Garza A*, Sinha A*, and Bowman TV. Hematopoietic stem cell origins: lessons from embryogenesis for improving regenerative medicine. Stem Cell Translational Medicine, 2017; 5:1-8.

24. De La Garza A*, Cameron RC*, Nik S, Payne SG, and Bowman TV. The Spliceosomal Component Sf3b1 is Essential for Hematopoietic Differentiation in Zebrafish. Experimental Hematology, 2016; 44(9): 826-31.

25. Flores-Figueroa E, Essers M, and Bowman TV. Hematopoiesis "awakens": evolving technologies, the force behind them. Experimental Hematology, 2016; 44(2): 101-5.

26. Bowman TV. Zebrafish Models to Study Stem Cells. The SAGE Encyclopedia of Stem Cell Research, Summer 2015.

27. Trompouki E, King KY, Will B, Lessard J, Flores-Figueroa E, Kokkaliaris K, and Bowman TV. Bloody signals: From birth to disease and death. Experimental Hematology, 2014; 42(12):989-94.

28. Bowman TV. Getting to the ncor of hematopoietic stem cell emergence. Blood, 2014; 124(10): 1541-2.