M.D., PhD
The Buck Family Professor in Hematology Director of the Comprehensive Bone Marrow Failure Center at The Children's Hospital of Philadelphia and Perelman School of Medicine University of Pennsylvania Health System Abramson Research Center 3615 Civic Center Blvd., Room 302

Diagnosis assessment an treatment of inherited and acquired Bone Marrow Failure
Acquired Aplastic Anemia
Familial Aplastic Anemia
Paroxysmal Nocturnal Hemoglobinuira
Diamond Blackfan Anemia
Shwachman Diamond Syndrome
Dyskeratosis Congenita
Other acquired and inherited bone marrow failure syndromes
Pediatric-Adult Transition of patents with bone marrow failure
Inherited Bone Marrow Failure in the Adult

Inherited and acquired bone marrow failure conditions

Research Interest:

Inherited and acquired bone marrow failure syndromes
Pathogenesis and genetics of clonal evolution in bone marrow failure
Telomere biology
Ribosome biosynthesis
Translational Research in Bone Marrow Failure
Pediatric ?Adult Transition
Comparative proteomics of the red blood cell in health and diease

Key words:

Aplastic anemia, myelodysplastic syndrome (MDS), Paroxysmal nocturnal hemoglobinuria (PNH), Dyskeratosis congenita, Diamond Blackfan Anemia (DBA), Shwachman Diamond Syndrome (SDS), Neutropenia, translational research, pediatric-adult transition, Orphan disease, genomics, proteomics, telomerase, ribosome biogenesis.

Research Projects 2012:

1. Defective telomere maintenance in bone marrow failure

2. Clonal evolution in bone marrow failure

3. Investigations of bone marrow failure syndromes using induced
pluripotent stem cells and mouse models.

4. Changes in the red cell proteome in health and disease

5. Pediatric?Adult Transition for patients with bone marrow failure

Description of Research:

Our research aims to define the molecular mechanisms that cause bone marrow failure and the factors that determine the clinical outcome and response to treatment. Bone marrow failure (BMF) is the inability of the bone marrow to produce sufficient blood cells. BMF may be brought about by a number of causes; these may be genetic (inherited bone marrow failure syndromes, IBMFS) or acquired. BMF may affect all, or only individual blood cell lineages. Our aims are a) to develop more specific tests or biomarkers that distinguish and diagnose individual forms of BMF, b) to identify the pathways that lead to BMF, c) to characterize the pathways responsible for late complications, such as the development of myelodysplastic syndrome (MDS) and leukemia, and finally d) to investigate specific and more targeted treatments for patients with BMF, allowing personalized therapy for patients with problems in blood cell production.

1. Defective telomere maintenance in bone marrow failure. Telomeres are complex protein DNA structures at the end of chromosomes. Defects in maintaining the proper telomere structure lead to cell cycle arrest and cell death. We are interested in defining the role of dysfunctional telomere maintenance in the pathogenesis of bone marrow failure and other clinical manifestations associated with Dyskeratosis Congenita, a rare bone marrow failure condition caused by excessively short telomeres.

2. We are interested in defining the early molecular events that determine recovery upon treatment, lack of treatment response, and early markers of malignant transformation, which is more frequent in some patients with specific forms of bone marrow failure. For this we will use high throughput sequencing technologies.

3. In collaboration with Philip J Mason, The Children?s Hospital of Philadelphia and Mitchell Weiss, Deborah L French, and Paul Gadue, Human ES/iPS Cell Core of The Children?s Hospital of Philadelphia we generate mouse and cellular models using induced pluripotent stem cells (iPSc) of specific BMF conditions, which allow us to investigate the pathways causing disease in a tissue and whole animal context. Animal models and tissue culture models allow us not only to investigate the pathways that cause disease but also to test for novel treatments that more specifically improve blood cell production in patients with BMF.

4. In collaboration with David Speicher at the Wistar Institute we are developing a robust, label-free proteomics platform allowing us to define differential protein expression in red blood cells. We are interested in using this platform to define changes in the red cell proteome that are specific for disorders caused by abnormal red blood cell production. This technology might not only allow us to define new diagnostic tools but possibly also to identify novel targets for therapy.

5. With improved therapy patients? with IBMFS live longer and become adults. Furthermore with the availability of genetic testing an increasing number of adult BMF patients are diagnosed with IBMFS, previously thought to be mainly a disease of childhood. Little is known about the clinical manifestations of IBMFS in adults, the course of disease and response to treatment. Our long-term goal is to build up a pediatric-adult transition program for patients with BMF, in order to determine the frequency, clinical manifestations, the course of disease, and treatment outcomes of IBMFS in the adult.

Professor of Medicine at University of Pennsylvania School of Medicine (2010 – 2015)
Adjunct Professor of Pediatrics at University of Pennsylvania School of Medicine (2015– present)
Professor of Pediatrics at University of Pennsylvania School of Medicine (2010 – 2015)
PhD, Genetics, University of London (1994)
M.D., University of Zurich, Switzerland (1981)
Selected Publications
Babushok DV, Li Y, Roth JJ, Perdigones N, Cockroft JD, Biegel JA, Mason PJ, Bessler M. Common polymorphic deletion of glutathione S-transferase theta predisposes to acquired aplastic anemia: Independent cohort and meta-analysis of 609 patients.. Am J Hematol. Vol 88(10) . 2013 October:862-867.
Babushok DV, Xie HM, Roth JJ, Perdigones N, Olson TS, Cockroft JD, Gai X, Perin JC, Li Y, Paessler ME, Hakonarson H, Podsakoff GM, Mason PJ, Biegel JA, Bessler M. Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes.. Br J Haematol. 2013 October:Epub head of print.
Garcon L, Ge J, Manjunath SH, Mills JA, Apicella M, Parikh S, Sullivan LM, Podsakoff GM, Gadue P, French DL, Mason PJ, Bessler M, Weiss MJ. Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients.. Blood. Vol 122(6) . 2013 August:912-921.