Dr Daria Babushok is a physician-scientist and an Assistant Professor of Medicine in the Division of Hematology-Oncology at the University of Pennsylvania. Dr Babushok laboratory conducts basic and translational research focusing on the immune pathogenesis of acquired aplastic anemia and the development of clonal hematopoiesis in acquired aplastic anemia and other bone marrow failure disorders.
Babushok Laboratory
The long-term goal of the Babushok Laboratory to improve the outcomes of patients with bone marrow failure disorders through bench-to-bedside research aimed at elucidating mechanisms of hematopoietic failure and transforming this knowledge into rational therapies. In our previous studies, we have established an analytical platform that sensitively and reliably identifies somatic changes in hematopoietic cells of patients with bone marrow failure using comparative whole exome sequencing (WES), single nucleotide polymorphism array (SNP-A) analysis, and deep targeted sequencing of the Major Histocompatibility Complex (MHC) region, and have used this pipeline to define the landscape of clonal hematopoiesis in acquired aplastic anemia (AA) and other bone marrow failure disorders. Our results led to novel insights into clonal evolution in patients with AA, and specifically, in the role of Human Leukocyte Antigen (HLA) Class I autoimmunity in the pathogenesis of AA. Based on our studies as well as studies of others, we hypothesize that bone marrow aplasia in AA is caused by autoreactive T cells that are directed against one or a small number of shared autoantigens presented by HLA class I alleles, and that this cytotoxic T cell attack, as well as its associated proinflammatory marrow environment, create a selective pressure that causes outgrowth of cells bearing adaptive somatic mutations. These mutations, in turn, affect the patients’ long-term outcomes, and some of them predispose to the development of MDS.
Our current studies aim to answer the following questions:
- What causes the emergence of clonal hematopoiesis in premalignant conditions, such as aging, inherited bone marrow failure syndromes, and immune-mediated bone marrow failure
- How can we use our knowledge of mechanisms of clonal selection to shift the balance in favor of healthy hematopoiesis?
- What is the pathogenic mechanism of acquired immune-mediated bone marrow failure (e.g. AA)?
- How can we transform the improved understanding of the immune pathogenesis of AA into novel prevention strategies, improved diagnostic tests, and rational therapies?
How do the mechanism of autoimmunity and immune evasion in AA inform our understanding of related phenomena, including immune surveillance and immune evasion in cancer and mechanisms of resistance to immunotherapies?
Location: Abramson Research Center, ARC 303
People
Benjamin Frost
Research Scientist
Ben received his Bachelor of Science degree in Chemistry from Haverford College in 2019. Before becoming a Research Specialist, Ben worked in the Comprehensive Bone Marrow Failure Center as an undergraduate, and he wrote one of his undergraduate theses on research related to acquired aplastic anemia. The scope of his research has since broadened to include other bone marrow failure disorders such as paroxysmal nocturnal hemoglobinuria.
Melissa Colden
Research Scientist
Melissa focused on public health and nutrition throughout undergrad and spent free time in the chemistry lab. After graduating in 2013, she did volunteer research at the San Francisco VA Medical Center studying the roles of miRNAs in prostate cancer and developed a skillset in molecular biology.
An Steensels
Research Scientist
An has a Master of Science in Biology from the University of Leuven in Belgium, and did a master thesis project on the contributions of ARF6 and Presenillins in endosomal trafficking in Alzheimer’s Disease. After graduating in 2015, she lived in Tanzania, Spain, and Belgium, where she worked on several science and animal rescue projects. In addition, An went back to school to get a degree in Veterinary Technology.
Research
The long-term goal of the Babushok Laboratory to improve the outcomes of patients with bone marrow failure disorders through bench-to-bedside research aimed at elucidating mechanisms of hematopoietic failure and transforming this knowledge into rational therapies.
Publication Highlights
Articles
Postdoctoral Fellow Opening
Tuesday, February 5, 2019 Full Article: view
The Babushok laboratory seeks an enthusiastic and dedicated Ph.D. or M.D./Ph.D. scientist to join our laboratory as a Post-Doctoral Fellow at the Perelman School of Medicine University of Pennsylvania. The Babushok laboratory performs cutting-edge translational research at the interface of hematology, immunology and molecular genetics to interrogate the mechanisms of acquired and inherited bone marrow failure and the link between bone marrow failure and leukemia. We recently identified a critical connection between the development of clonal hematopoiesis in immune-mediated bone marrow failure called aplastic anemia and somatic loss of specific HLA class I alleles, shedding light on the mechanism of the autoimmune attack in this disease. Research opportunities are available investigating various facets of the immune mechanism of aplastic anemia. The studies will utilize a variety of cutting-edge proteomics and immunogenetic approaches, including mass spectrometry-based proteomic analyses of immune epitopes, next-generation sequencing analyses of HLA and TCR genes, use of genetic engineering technologies to create cell lines bearing designer TCR and HLA alleles, CRISPR-based cell culture models, cytotoxicity assays, RNA interference and pharmacologic inhibition of involved pathways using in vitro and murine models.