Yupo Ma, MD, PhD

Yupo Ma, MD, PhD
Medical Director of Flow Cytometry Lab
Scientific Director of Stem Cell Core
Program Director for Hematopathology Fellowship

Basic Sciences Tower, Level 9
Stony Brook Medicine
Stony Brook, NY 11794-8691

Phone: (631) 444-3000
Fax: (631) 444-3424
Email: Yupo.Ma@stonybrookmedicine.edu

Dr. Ma earned his Medical Degree from Jinan University (P.R. China), College of Medicine and a Ph.D. from the University of South Alabama College of Medicine. He completed a residency in Pathology at Brown University, clinical fellowship in Hematopathology at M.D. Anderson Cancer Center and has conducted Post Doctoral Training in Pathology at Harvard Medical School.  Dr. Ma joins the Department as a hematopathologist and serves as Professor of Pathology and Medical Director of the Flow Cytometry Laboratory.  Formerly, he was Chief of Hematopathology, Head of the Stem Cell Program, and Director of the Flow Cytometry Laboratory at Nevada Cancer Institute.

Research Interests:

1. Leukemic stem cells.
We focus on the role of SALL4 in pluripotent progenitor cells and leukemic progenitor cells. The SALL gene family is the mammalian homologue of Drosophila gene Spalt (sal).  In Drosophila, sal mutation can lead to the incomplete separation of the head and trunk of the fly. In the human, heterogeneous mutation of SALL1 causes Townes-Brock Syndrome with renal, cardiac, genital malformation.  Heterogeneous mutation of SALL4 in humans is associated with Okihiro Syndrome with limitation of eye abduction, deafness, and digit malformation.

Recent works has suggested that SALL4 plays important roles during development.  SALL4 plays an important role in the maintenance of pluripotent properties and self renewal during mammalian development.  Consistently, SALL4 is able to bind to both OCT4 and NANOG.  Loss of SALL4 expression results in cellular differentiation.

We have demonstrated that SALL4 is constitutively expressed in acute myeloid leukemias (AML) and fails to turn off in nearly all human AMLs.  A fundamental unanswered question: is constitutive expression of SALL4 sufficient to induce AML?  In addition, what mechanisms of SALL4 induce AML?  How does SALL4 promoter leukemic progenitor cell self renewal?  We have chosen a mammalian model system to approach these questions.  This should allow us to test directly leukemogenic potential of constitutive expression of SALL4 in .  A mammalian model overexpressing SALL4 develops hematopoietic disorders including myelodysplastic-like symptoms and subsequently acute myeloid leukemia.  The constitutive expression of SALL4 is causal to the leukemic phenotype and SALL4 may interact with the Wnt/β-catenin pathway in the leukemogenesis.  Our mammalian models should provide a useful platform to analyze the effect of SALL4 on hematopoiesis and its potential cooperation with Wnt/β-catenin pathway in the pathogenesis of leukemia progenitor cells.  Leukemic progenitor cells are aberrant cells that maintain and propagate blood cancers.

A parallel project involves an investigation of the SALL4 function in development and hematopoiesis.  We are creating a loss of function model for SALL4 using conventional and conditional knockout approaches. In characterizing the phenotype of SALL4 deficient models, we are focusing on the role of SALL4 in regulating hematopoiesis and hematopoietic progenitor cell function. 

2. Stem cell therapy and tissue repair.
Our recent studies are also focused on a stem cell therapy by using adult somatic cells and turning back the development of these cells so they act like embryonic cells. This process, called retrodifferentiation, produces pluripotent stem cells. These induced pluripotent stem cells (iPS cells) in combination with growth factors can then be redifferentiated into cells which may be used to treatment specific diseases. In this case, the iPS derived cells function in the animal to synthesize a protein (clotting factor that has shown it can reverse excessive bleeding, which may eventually be useful for treating hemophilia patients. Our lab is the first to document the ability to “cure” mice with Hemophilia A by a single injection of endothelial cell precursors derived from iPS cells.  Using similar strategies, our lab has generated a variety of differentiated cell types including hematopoietic cells, liver hepatocytes, pancreatic islet cells,  heart cells, lung cells, and various neuronal cell types.  These will be tested in various therapeutic model systems in the near future.

Peer Reviewed Publications: