Jonathan G. Hoggatt, PhD
Senior Investigator/Head, Hoggatt Lab, CTS
Assistant Professor of Medicine
Massachusetts General Hospital
Center for Transplantation Sciences
Harvard Medical School
Center for Cancer Research
Explore the Hoggatt Lab
The Hoggatt laboratory is broadly interested in the stem cell niche regulatory mechanisms that govern tissue regeneration, and we have a specific interest in translational science for bone marrow transplantation and other treatments. Our laboratory identified a unique “highly engraftable” hematopoietic stem cell that we are currently investigating which has applications for further probing of stem cell niche biology, and clinical applications in transplantation, gene therapy, and other fields. We have also recently discovered a method to prevent hair graying following DNA damage, with not only potential to translate to the clinic, but gives a strong tool to study cancer resistance mechanisms.
Hematopoietic Stem Cell Biology
Hematopoietic stem cell (HSC) transplantation is used to treat a number of malignant and non-malignant diseases. Over the last decade, there has been increasing evidence that the HSC pool is heterogeneous in function; with identification of HSCs with differing lineage outputs, kinetics of repopulation, length of life-span, and perhaps differences amongst HSCs contributing to homeostatic blood production from those that are the engraftable units in transplantation. Delineating the mechanisms of these functional differences has the potential to increase the efficacy of stem cell transplantation.
Currently, there are no great methods for prospectively isolating differing HSC populations to study heterogeneity; much of the data that has been acquired is based on clonal tracking, single cell transplantation, etc. We have developed a rapid mobilization regimen as a new method to acquire HSCs. Fifteen minutes after administering a single subcutaneous injection in mice, stem cell mobilization to the blood is greater than five days of granulocyte-colony stimulating factor (G-CSF) treatment; the current gold standard for hematopoietic mobilization. Surprisingly, when equivalent numbers of highly-purified HSCs from the blood of mice treated with the rapid regimen versus G-CSF were subsequently competitively transplanted into lethally irradiated recipients, the HSCs mobilized by the rapid regimen substantially outperformed those mobilized by G-CSF. The rapid regimen mobilizes a “highly engraftable” hematopoietic stem cell (heHSC) compared to those mobilized by G-CSF.
Much like panning for gold, we have used the differential mobilization properties of our regimen and G-CSF as a “biologic sieve” to isolate the heterogeneous HSC populations from the blood. Our laboratory will continue to leverage this approach to analyze the transcriptomic and epigenetic differences between the two populations of HSCs to determine the specific gene(s) that account for the heHSC phenotype, and to further explore the biologic potential of this new population of stem cells. These efforts have the potential to substantially increase our knowledge of heterogeneity and increase efficacy of HSC based clinical therapies.
Prevention of Hair Graying
At least 50% of all human cancers are treated using radiation with curative intent. The goal of this radiotherapy is to eliminate all of the cancer stem cells within a tumor and the nearby lymph nodes. However, many cancers are, or become, resistant to radiation, reducing the effectiveness of the treatment. To enhance these therapies, a detailed understanding of the cellular response to radiation is needed. Melanoma is one of the most radio-resistant cancers, and as such, we propose that melanocytes and their stem cells are the perfect model system to explore how a cell protects itself from an otherwise lethal hit of ionizing radiation. In a series of unrelated experiments in hematopoiesis, we recently discovered a method to prevent irradiated mice from turning gray. Understanding the mechanisms involved in this finding will allow us to identify novel molecules with activity on melanocytes, and allow for identification of radio-resistance pathways to explore in melanoma, and general cancer.
Email your curriculum vitae, statement of interest and career goals, and names and contact information of at least three references to Jonathan Hoggatt, PhD.
Czechowicz A, Palchaudhuri R, Scheck A, Hu Y, Hoggatt J, Saez B, Pang WW, Mansour MK,Tate TA, Chan YY, Walck E, Wernig G, Shizuru JA, Winau F, Scadden DT, Rossi DJ. Selective hematopoietic stem cell ablation using CD117-antibody-drugconjugates enables safe and effective transplantation with immunity preservation. Nature Communications, 2019; Feb6;10(1):617-628.
Hoggatt J*, Singh P, Tate TA, Chou BK, Datari SR, Fukuda S, Liu L, Kharchenko PV, Schajnovitz A, Baryawno N, Mercier FE, Boyer J, Gardner J, Morrow DM, Scadden DT, Pelus LM. Rapid mobilization reveals a highly engraftable hematopoietic stem cell. Cell, 2018; Jan11;172(1- 2):191-204.
Hoggatt J. Gene Therapy for ‘Bubble Boy’ Disease. Cell, 2016; Jul 14;166(2):263.
Palchaudhuri R, Saez B, Hoggatt J, Schajnovitz A, Sykes DB, Tate TA, Czechowicz A, Kfoury Y, Ruchika F, Rossi DJ, Verdine GL, Mansour MK, Scadden DT. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nature Biotechnology, 2016; Jul;34(7):738-45
Hoggatt J, Kfoury Y and Scadden DT. Hematopoietic Stem Cell Niche in Health and Diseases. Annual Review of Pathology, 2016;11:555-581.
Hoggatt J†*, Hoggatt AF†*, Tate TA, Fortman J, Pelus LM*. Bleeding the Laboratory Mouse: Not All Methods are Equal. Experimental Hematology, 2016: Feb;44(2):132-137.
*Lead corresponding author
After exposure to radiation, melanocyte stem cells are exhausted and hair turns gray. New work in the Hoggatt laboratory has now identified a method to prevent hair graying, and is being used as a model to study mechanisms of resistance to cancer treatment.
Jonathan G. Hoggatt, PhDPrincipal Investigator
- Aurelia Bleinroth
- Bin-Kuan Chou, PhD
- Juan Menendez Gonzalez, PhD
- Sana Shareef