Mapara Lab

Location and Contact Information

161 Fort Washington Ave, New York, NY 10
New York, NY 10032
United States

Principal Investigator

  • Profile Headshot
    • Director, Adult Blood and Marrow Transplantation Program, Columbia University Medical Center

The Mapara Lab's research is primarily focused on developing new approaches to improve the outcome of patients undergoing hematopoietic stem cell transplantation.

The following research areas are being investigated:

Role of Interferon-g(IFN- g) Signaling in controlling GVHD and GVL

Our lab was the first to show impairing type I and II interferon signaling in donor T cells through abolishing STAT1 attenuates the development of Graft versus Host Disease (GVHD) in murine BMT models. These studies provided the rationale for testing of JAK1/2 inhibitors for the treatment and prevention of GVHD in the clinical setting by other groups and ultimately led to the approval of JAK inhibitors for the treatment of refractory acute and chronic GVHD. Furthermore, interfering with IFNg-receptor/STAT1 signaling promoted expansion of nTreg and iTreg. Our lab is now focusing on using gene-editing approaches to target the IFNgR signaling pathway to numerically and functionally enhance human Tregs.

Molecular Computing for graft engineering and redirecting of immune effector cells (in collaboration with Sergei Rudchenko and Milan Stojanovic)

Selective enrichment or depletion of complex cell populations based on the combination of several cell surface markers is a highly desirable goal in cell therapy, because it can minimize side-effects of allogeneic hematopoietic stem cell transplantation (aHSCT). We developed molecular computing cascades that evaluate in a single step multiple surfaces markers and label narrow populations of cells for elimination. Using ex and in vivo benchmarks and clinically relevant humanized xenogenic mouse graft-vs-host disease (GVHD) models, we have shown the translational potential  of such a graft engineering approach for allogeneic BMT (e.g eliminating naïve (CD45RA) T cells while sparing other CD45RA-expressing cells (eg. B, NK cells).

Deceased donor bone marrow as source for HSC in clinical transplantation

Availability of matched HSC donors remains a major barrier especially for patients from under-represented minorities. Approaches to overcome donor shortage include finding other HSC e.g. umbilical cord blood. Harvesting HSC from bone marrow (BM) of cadaveric donors has not been established or validated for clinical HSCT but may be of high relevance to expand the pool of HSC and may be of significant value for induction of immunological tolerance in the setting of combined organ and bone marrow transplantation. The objective of our studies is to perform in-depth characterization of deceased donor bone marrow and to functionally investigate whether CD34+HSC selected from Cadaveric Bone Marrow Cells (CBMC) have retained the capacity for long term engraftment.

Role of MMP-13 in regulating allo-immunity (in collaboration with Suzanne Lentzsch)

Matrix metalloproteinases (MMPs) have been initially recognized for their role in degradation of extracellular matrix (ECM) and collagen remodeling. However, MMPs have been shown to play a crucial role in inflammation, tumor cell invasion, adaptive and innate immunity. Acute and chronic Graft versus Host Disease (GVHD) are characterized by distinctive histopathological features involving tissue infiltration with donor cells, tissue damage and remodeling. We therefore hypothesized that GVHD-associated organ damage may involve MMPs. We have now identified a novel immunomodulatory function for MMP-13 (alternatively called collagenase-3) and have uncovered a previously unknown role of MMP-13 in regulating GVHD. MMP-13 deficiency in either splenocytes or bone marrow-derived dendritic cells used as stimulators resulted in enhanced proliferation, activation and IFN- g production in alloreactive lymphocyte responder cells. Similarly, absence of MMP-13 in recipient mice significantly accelerated donor cell expansion. Current studies are ongoing to determine the underlying mechanisms.