Our current bench research is aimed at understanding the stem cell defects in Fanconi anemia (FA) and Shwachman-Diamond syndrome (SDS), two of the most commonly seen inherited bone marrow failure syndromes (IBMFS). These disorders share common pathophysiologic features with each other and predispose to the development of acute myeloid leukemia and cancer. Thus, while rare, these diseases serve as human genetic models of hematopoietic failure and cancer predisposition and may reveal insights into fundamental stem cell biology.  In studies aimed at elucidating the tumor suppressor function of FA proteins, our laboratory has discovered that FA oncogenesis may reflect escape from an activated tumor suppressor checkpoint.  In studies of the Shwachman-Diamond syndrome SBDS gene orthologs, our collaborators and we have uncovered a potential role for SBDS in ribosome function. These findings may link the pathophysiology of Shwachman-Diamond syndrome with that of Diamond Blackfan anemia (DBA), another IBMFS that results from haploinsufficiency of ribosomal proteins. Our laboratory is actively engaged in research on the so-called stem cell niche, which is the stromal compartment that supports and maintains hematopoietic stem cells.  We are conducting ongoing experiments to assess the contribution of the stromal compartment to growth and expansion of both normal and leukemia stem cells. Finally, under the supervision of Dr. Jeffrey Lipton, we are also involved in translational research on pediatric brain tumors.

The Les Nelkin Memorial Pediatric Oncology Lab has close ties with the Diamond-Blackfan Anemia Registry (DBAR), which tracks the genetic and clinical histories of over 500 DBA patients. The DBAR was established and is maintained by Drs. Adrianna Vlachos and Jeffrey Lipton.

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Lab Members:

Name:   Adrianna Vlachos, MD
Position:   Co-Principal Investigator
Research:   Co-directs the Diamond-Blackfan Anemia Registry (DBAR) of North America.
E-mail:   avlachos@nshs.edu

Name:   Jeffery M. Lipton, PhD
Position:   Co-Principal Investigator
Research:   Co-directs the Diamond-Blackfan Anemia Registry (DBAR) of North America.
E-mail:   jlipton@nshs.edu

Name:   Sarah Vaiselbuh, MD
Position:   Pediatric Hematology/Oncology Fellow
Research:   Studies stem cells and the tumor microenvironment.

Name:   Gulay Sezgin, MD
Position:   Postdoctoral Research Fellow
Research:   Studies Shwachman-Diamond syndrome.
E-mail:  gsezgin@nshs.edu

Name:   Sharon Singh, MD
Position:   Pediatric Hematology/Oncology Attending
Research:   Studies Diamond Blackfan anemia.
E-mail:   ssingh@nshs.edu

Name:   Eva Atsidafto, MA
Position:   Research Associate
Research:   Co-directs the Diamond-Blackfan Anemia Registry (DBAR) of North America.
E-mail:   eatsidaf@nshs.edu

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Publications 2006-2008

Liu JM, Ellis SR: Ribosomes and marrow failure: coincidental association or molecular paradigm? Blood 107:4583-4588, 2006.

Stein MN, Shin J, Gudzowaty O, Bernstein AM, Liu JM: Antibody-dependent cell cytotoxicity to breast cancer targets despite inhibitory KIR signaling.  Anticancer Res 26:1759-1764, 2006.

Yamamoto K, Nihrane A, Aglipay J, Sironi JJ, Arkin S, Lipton JM, Ouchi T, Liu JM: Upregulated ATM gene expression and activated DNA crosslink-induced damage response checkpoint in Fanconi anemia:  implications for carcinogenesis. Mol Med 14:167-174, 2008.

Vlachos A, Ball S, Dahl N, Alter BP, Sheth S, Ramenghi U, Meerpohl J, Karlsson S, Liu JM, LeBlanc T, Paley C, Kang E, Judmann Leder E, Atsidaftos E, Shimamura A, Bessler M, Glader B, Lipton JM: Diagnosing and treating Diamond Blackfan anemia: results of an international clinical consensus conference Br J Haematol 142:859-876, 2008.

Nihrane A, Sezgin G, Dsilva S, Dellorusso P, Yamamoto K, Ellis SR, Liu JM: Depletion of the Shwachman-Diamond syndrome gene product, SBDS, leads to growth inhibition and increased expression of OPG and VEGF-A. Blood Cells Mol Dis 42:85-91, 2009.

Book Chapters

Otsuki T, Liu JM. Other proteins and their interactions with FA gene products. In Molecular Mechanisms of Fanconi Anemia, Ahmad SI, Kirk SH, eds., Eurekah.com eBook and Springer/Landes Bioscience, 2006.

Liu JM, Dokal I. Constitutional aplastic anemias. In Clinical Hematology, Young NS, Gerson SL, High KA, eds. Elsevier, Philadelphia, p. 158-168, 2006.