Broxmeyer Lab

The research lab of Hal E. Broxmeyer, PhD is studying the mechanisms regulating proliferation, survival, self-renewal, metabolism, differentiation and homing/mobilization of hematopoietic, embryonic and induced pluripotent stem cells at cellular, intracellular and animal levels, as well as gene transfer, to influence these functions.

Investigators in the Broxmeyer Lab at IU School of Medicine are interested in blood cell production (hematopoiesis) in the context of normal and abnormal cell regulation as assessed in vitro and in vivo. As a clinical correlate, this laboratory is exploring the use of hematopoietic stem and progenitor cells, especially those from umbilical cord blood, for transplantation purposes, and the use of cytokines/chemokines for treatment of hematological disorders.

Active Research

Transplantation

The Broxmeyer Lab has been involved in studies assessing and establishing the use of cord blood for transplantation and in vivo effects of cytokines, especially in patients on clinical trial. Investigators in this lab demonstrated that inactivation/deletion of the peptidase activity of CD26/Dipeptidylpeptidase (DPP) IV on murine and human stem cells greatly enhances their homing and engraftment capability (clinical trials are ongoing to use this to enhance engraftment of cord blood cells) and that DPPIV can truncate and change the activity of a number of growth regulating factors. They have demonstrated the potent stem and progenitor cell mobilizing capacity of AMD3100, an antagonist of SDF-1/CXCL12 binding to its receptor CXCR4, that led the clinical trials with AMD3100 in this context.

Most recently they demonstrated that removal of hematopoietic stem cells under ambient air, as everyone does, acts as a strong stress that immediately differentiates them and this greatly reduces their numbers, and that reduction of this stress results in greatly enhanced recovery of numbers of transplantable stem cells. They have also found new means to ex-vivo expand hematopoietic stem cells and to enhance their homing and engrafting capabilities.

Metabolism and Mitochondria

The laboratory also studies maintenance and hematopoietic differentiation of embryonic and induced pluripotent stem cells. Intracellular signal transduction studies are utilized to evaluate mechanisms of cell proliferation and survival, mobilization of cells from the marrow to the blood, and homing from blood to marrow. This includes viral-gene transfer approaches. Mice in which specific genes are either deleted or inserted are utilized to determine dominant regulatory effector proteins. Recent studies have focused on: metabolism and mitochondria.

Research Funding

5R01 HL056416-19 (Broxmeyer) NIH/NHLBI, 04/01/1996 – 4/30/2018, 1.80 calendar
This grant focuses on a role for SIRT1 in regulation of hematopoiesis, and in intracellular mechanisms involved in multiple growth factor-induced synergistic stimulation of the proliferation of stem/progenitors.
Role: PI

1R01 HL112669-05 (Broxmeyer and Farag, multi-PI) NIH/NHLBI, 03/01/2012 – 02/28/2018, 1.80 calendar
The aims are to: (1) determine mechanisms involved in regulation of cytokine/chemokine actions/activity by CD26, a cell surface enzyme, Dipeptidylpeptidase (DPP) 4 and (2) assess inhibition of DPPIV activity by the orally active inhibitor, sitagliptin in recipients with end stage malignancy treated by single cord blood transplantation in a multi-center clinical trial.
Role: PI in Multi-PI grant

5T32 HL007910-18 (Broxmeyer) NIH/NHLBI, 07/01/1999 – 08/31/2019, .60 calendar (cost share)
This is a training grant for Pre- and Post-Doctoral Students.
Role: PI

1U54DK106846-02, Broxmeyer (PI); Srour (Co-PI) NIH/NIDDK, 09/30/2010 – 06/30/2020, .37 calendar
This grant, a Cooperative Center of Excellence in Hematology (CCEH) Award, only supports core facilities to understand and correct, at the molecular level, genetic diseases affecting cells derived from hematopoietic stem cells. This was previously funded as 1P30 DK090948.
Role: PI

DEK Regulation of Hematopoietic Stem Cell Renewal, Fate, and Hematopoiesis, $955,319
1R01DK109188-01 (Broxmeyer/Markovitz) NIH/NIDDK, 07/01/2016 – 05/31/2020, 1.80 calendar (1.11 charged to grant)
This grant investigates the role of DEK in regulation of hematopoietic stem cells.
Role: Co-PI (Multi-PI grant)

5T32 DK007519-31 (Broxmeyer), NIH/NIDD, 07/01/1985 – 06/30/2021, .60 calendar (cost share)
This is a training grant for Pre- and Post-Doctoral Students.
Role: PI

R35 HL139599 (Broxmeyer), NIH/NHLBI, 12/01/2017 – 11/30/2014, 6.0 calendar
The lab proposes to study the mechanistic effects of oxygen tension and the enzymatic activities of CD26/Dipeptidylpeptidase (DPP)4 on hematopoietic stem and progenitor cells during stress, aging, and disease for their modulation for health benefit.
Role: PI

Recent Publications

O’Leary, Capitano, M.L., Cooper, S., Mantel, C., Boswell, S., Kapur, R., Ramdas, B., Chan, R., Deng, L., Skinner, H.D., Qui, C.K., and Broxmeyer, H.E. 2016. DPP4 truncated GM-CSF and IL-3 manifest distinct receptor binding and regulatory functions compared to their full length forms. Leukemia. 2017 Apr 21. doi: 10.1038/leu.2017.98. [Epub ahead of print]. NIHMSID 861032

Aljitawi, O.S., Paul, S., Ganguly, A., Lin, T.L., Ganguly, S., Vielhawer, G., Capitano, M.L., Cantelina, A., Lipe, B., Mahnken, J.D., Wise, A., Berry, A., Singh, A., Shune, L., Lominska, C., Abhyankar, S., Allin, D., Laughlin, M., McGuirk, J.P., and Broxmeyer, H.E. 2016. Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation. Blood. 128(25):3000-3010. PMCID: PMC5179334 [Available on 2017-12-22]

Guo, B., Huang, X., Cooper, S., and Broxmeyer, H.E. 2017. Glucocorticoid hormone promotes human hematopoietic stem cell homing and engraftment by chromatin remodeling. Nat Med. 23(4):424-428.

Park, S-J., Prasain, N., Lee, S.A., Bae, D., Kang, H., Ha, T., Kim, J.S., Hong, K-S., Mantel, C., Moon, S-H., Broxmeyer, H.E., and Lee, M.R. 2017. Metabolome profiling of partial and fully reprogrammed iPSCs. Stem Cells Dev. 26:734-742.

Broxmeyer, H.E., Capitano, M. Campbell, T., Hangoc, G., and Cooper, S. 2016. Modulation of hematopoietic chemokine effects in vitro and in vivo by DPP4/CD26. Stem Cells and Development. 25:575-585. PMCID:PMC4834524 [Available on 2017-04-15]

Lee, M.R., Mantel, C., and Broxmeyer, H.E. 2016. Mir-31/SDHA axis regulates reprogramming efficiency through mitochondrial metabolism. Stem Cell Reports. 7(1):1–10. PMCID: PMC4944586

Mantel, C.R., O’Leary, H.A. Chitteti, B.R., Huang, X., Cooper, S., Hangoc, G., Brustovetsky, N., Srour, E.F., Lee, M.R., Messina-Graham, S., Haas, D.M., Falah, N., Kapur, R., Pelus, L.M., Bardeesy, N., Fitament, J., Ivan, M., Kim, K-S., and Broxmeyer, H.E. 2015. Enhancing hematopoietic stem cell transplantation efficacy by mitigating oxygen shock. Cell. 161:1553-1565. PMC4480616 [Available on 2016-06-18]

Guo, B., Huang, X., and Broxmeyer, H.E. 2016. Antagonizing PPARγ-FBP1 axis-repressed glycolysis expands human haematopoietic stem cells. Nature Medicine. Accepted.

Capitano, M.L., Hangoc, G., Cooper, S., and Broxmeyer, H.E. 2015. Mild heat treatment primes human CD34+ cord blood cells for migration towards SDF-1 and enhances engraftment in an NSG mouse model. Stem Cells. 33(6):1975-1984. PMC4441568 [Available on 2016-06-01]

Huang, X., Lee, M.R., Cooper, S., Hangoc, G., Hong, K-S., Chung, H-M., and Broxmeyer, H.E. 2015. Activation of OCT4 enhances ex vivo expansion of human cord blood hematopoietic stem and progenitor cells by regulating HOXB4 expression. Leukemia. 30:144-153. PMC4703453 [Available on 2016-07-01]

Faculty Research Team

Hal E. Broxmeyer, PhD

Hal E. Broxmeyer, PhD

Distinguished Professor
Maegan L. Capitano, PhD

Maegan L. Capitano, PhD

Assistant Research Professor of Microbiology & Immunology
Bin Guo, PhD

Bin Guo, PhD

Postdoctoral Fellow in Microbiology & Immunology
Xinxin Huang, PhD

Xinxin Huang, PhD

Postdoctoral Fellow in Microbiology & Immunology
Samisubbu R. Naidu, PhD

Samisubbu R. Naidu, PhD

Assistant Research Professor of Microbiology & Immunology

Additional Research Team Members

Other research team members in the Broxmeyer Lab include Arafat Aljoufi, MD (PhD Graduate Student); Qingchun Cai, PhD (Research Associate), Scott Cooper (research associate), Itee Sharma, MS (Masters Student), Thao Le Phuong Trinh, BS (MD/PhD Student).