Hoggatt Laboratory

The Hoggatt Laboratory is broadly interested in the stem cell niche regulatory mechanisms that govern tissue regeneration, particularly regulation by macrophages, and has a specific interest in translational science for bone marrow transplantation and other treatments.

Our laboratory has identified a unique “highly engraftable” hematopoietic stem cell that has applications for further probing of stem cell niche biology, and clinical applications in transplantation, gene therapy  and other fields. We have also developed unique genetic mouse models allowing us to dynamically explore macrophage heterogeneity in a variety of disease settings.

Principal Investigator

Jonathan Hoggatt, PhD
Assistant in Immunology, Department of Medicine, Massachusetts General Hospital
Instructor in Medicine, Harvard Medical School

Jonathan Hoggatt, PhD, received his bachelor’s degree from Purdue University in pharmaceutical sciences and his master’s degree in biology from Indiana University. He then studied in the Department of Microbiology and Immunology at Indiana University School of Medicine, receiving his doctorate in hematology. His dissertation was awarded the Esther L. Kinsley award, the highest honor bestowed amongst doctoral work across all disciplines. Dr. Hoggatt then trained during a post-doctoral fellowship with David Scadden at Harvard University and Massachusetts General Hospital from 2011-2015.

Dr. Hoggatt is an assistant professor of medicine at Harvard Medical School and Massachusetts General Hospital in both the Center for Transplantation Sciences and the Cancer Center. He is also a principal faculty member in the Harvard Stem Cell Institute and an affiliate faculty member of the Stem Cell and Regenerative Biology Department at Harvard University, where he teaches immunology. His research is translationally focused and has resulted in a number of clinical trials. His laboratory investigates the regulation of hematopoietic stem and progenitor cells, and he is interested in developing methods that facilitate engraftment and mobilization for transplant.

Dr. Hoggatt also serves on the American Society of Hematology’s Committee of Government Affairs and Communications Committee and is a contributing editor to The Hematologist. He is a former police commissioner and city councilman. Learn more
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Laboratory Manager
Shruti Datari

Harvard University Undergraduate Researcher
Hannah Rasmussen

Post-Doctoral Fellow
Bin-Kuan Chou, PhD

The Hoggatt Laboratory leads the following projects:

• Macrophage Regulation of Tissue Regeneration: Macrophages are ancient cells of the innate and adaptive immune system. White blood cells that routinely phagocytizing dead cells and debris, they are integral to the immune response to foreign bodies, such as infectious microorganisms.
  
  Tissue resident macrophage populations exist in virtually every tissue, whether they are Kupffer cells in the liver, alveolar macrophages in the lung, microglia in the brain or Langerhans cells in the skin. Some of these macrophages have been recently reported to specify hepatic progenitor cell fate, regulate epithelial progenitor niches in the colon and drive oligodendrocyte differentiation during remyelination in the central nervous system. After depletion of macrophages, an adult salamander is unable to regenerate an amputated limb. However, when macrophage levels were allowed to replenish, full limb regeneration capacity of failed stumps was restored upon re-amputation. Macrophages, therefore, may be a common cellular regulator across a diverse repertoire of stem cell niches. The problem that exists today is that macrophages are extraordinarily diverse and plastic, necessitating the need to identify specific subsets responsible for stem cell and tissue regeneration, in both homeostatic and disease scenarios.
  
  We have created a unique mouse model that allows tracking of macrophages with deferring embryonic origins with specific, genetic-fluorescent markers, aiding in de-convoluting this heterogeneous cell population. Our laboratory is exploring several clinically relevant applications for stem cell transplantation and will broadly use these macrophage tools and knowledge to delineate macrophage regenerative signals in multiple tissue stem cell niches, organ transplantation and disease
• 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 a single subcutaneous injection in mice leads to mobilization that 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 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.

Email your curriculum vitae, statement of interest and career goals, and names and contact information of at least three references to Jonathan Hoggatt, PhD