Adelman presents at the 2016 MCP Symposium.Molecular and Cellular Pathology graduate Program student, Emmalee Adelman, successfully defended her PhD thesis on April 9. Widespread epigenetic reprogramming in aging human hematopoietic stem cells, covers her work in the lab of her mentor, Ken Figueroa, MD.
Adelman’s abstract states, “At the root of the hematopoietic hierarchy reside the Janus- faced hematopoietic stem cells (HSC), capable of both self- renewal and differentiation. Aging impairs HSC function, leading to increased self-renewal, reduced homing ability and a myeloid differentiation bias. In addition, hematopoietic cells acquire somatic mutations as they age, frequently affecting epigenetic modifier genes.
In this dissertation work, I provide a comprehensive characterization of epigenomic changes during normal human HSC aging and demonstrate that aged HSCs undergo widespread reduction in H3K27ac, H3K4me1 and H3K4me3, with little change in H3K27me3. Age-associated loss of enrichment of the activating histone marks H3K27ac and H3K4me3 was particularly prominent at active enhancers and bivalent promoters, respectively.
Functional annotation of enhancers lost with age suggests that enhancer deregulation may contribute to HSC myeloid bias and the immune impairments observed in older individuals. Focal changes in DNA methylation were also observed with age, affecting WNT and cadherin associated pathways, and at regions that may predispose to leukemogenesis. DNA 5-hydroxymethylation displayed age-related gains, targeting GATA and KLF binding sites.
Concurrent with these epigenetic changes were transcriptional downregulation and mis-splicing of epigenetic modifiers, spliceosome components, transcription factors, including many in the KLF family, and LMNA, which is mutated in Hutchinson-Gilford progeria syndrome.
Finally, single-cell RNA-seq of HSCs suggests that age-related epigenetic changes of HSC are due to reprogramming rather than the expansion of a pre-existing subpopulation. Together, these results establish that multiple levels of epigenetic deregulation with age converge on key hematopoietic regulatory genes and pathways contributing to aged HSC dysfunction.”
Adelman’s doctoral committee consisted of Co-Chairs Ken Figueroa, MD and Andrew Muntean, PhD, as well as Richard Miller, MD, PhD, Ivan Maillard, MD, PhD, and Yali Dou, PhD.
In addition to publications in Cell Stem Cell and Nature, Adelman was the recipient of many awards throughout her training, including the University of Michigan Department of Pathology Outstanding Poster Award in 2016, and the American Society of Hematology, Abstract Achievement Award in both 2016 and 2017.
ON THE COVER
Breast team reviewing a patient's slide. (From left to right) Ghassan Allo, Fellow; Laura Walters, Clinical Lecturer; Celina Kleer, Professor. See Article 2014Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Autopsy Technician draws blood while working in the Wayne County morgue. See Article 2016Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Dr. Sriram Venneti, MD, PhD and Postdoctoral Fellow, Chan Chung, PhD investigate pediatric brain cancer. See Article 2017Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Director of the Neuropathology Fellowship, Dr. Sandra Camelo-Piragua serves on the Patient and Family Advisory Council. 2018Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Residents Ashley Bradt (left) and William Perry work at a multi-headed scope in our new facility. 2019Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Dr. Kristine Konopka (right) instructing residents while using a multi-headed microscope. 2020Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Patient specimens poised for COVID-19 PCR testing. 2021Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Dr. Pantanowitz demonstrates using machine learning in analyzing slides. 2022Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
(Left to Right) Drs. Angela Wu, Laura Lamps, and Maria Westerhoff. 2023Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Illustration representing the various machines and processing used within our labs. 2024Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
MLabs, established in 1985, functions as a portal to provide pathologists, hospitals. and other reference laboratories access to the faculty, staff and laboratories of the University of Michigan Health System’s Department of Pathology. MLabs is a recognized leader for advanced molecular diagnostic testing, helpful consultants and exceptional customer service.