Ryan Corces, PhD
Assistant Professor
Neurology
School of Medicine

Our long-term research interest is to use insights from the epigenome to inform our understanding of neurological disease with the goal of identifying novel avenues for therapeutic intervention. More specifically, we are interested in how the genome and epigenome intersect and how inherited genetic variation interfaces with lived experiences and environmental factors to produce durable and functional epigenetic alterations that lead to Alzheimer’s and Parkinson’s disease.

Alzheimer’s disease (AD) and Parkinson’s disease (PD) both manifest as devastating age-related progressive neurodegeneration. This neurodegeneration and the concomitant loss of cognitive function plagues more than 44 million individuals worldwide for AD and more than 10 million individuals worldwide for PD. Our understanding of the molecular pathogenesis of these diseases remains incomplete and no therapies exist to prevent, stop, or cure the associated neurodegeneration. This marks one of the greatest unmet clinical needs of our time and a looming global public health crisis. At the most basic level, neurodegenerative diseases such as AD and PD result from the wrong genes being expressed in the wrong ways at the wrong times. Moreover, these are diseases of age with most patients manifesting symptoms after age 70. This age-associated onset of symptoms indicates that in addition to the known genetic causes of neurodegeneration, there are also epigenetic underpinnings to these diseases. This leads to the hypothesis that understanding the epigenome in AD and PD has the potential to provide key insights that inform the development of novel therapies.

• Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial DNA.
  eLife 2019 Xu J, Nuno K, Litzenburger UM, Qi Y, Corces MR, Majeti R, Chang HY
• The chromatin accessibility landscape of primary human cancers.
  Science (New York, N.Y.) 2018 Corces MR, Granja JM, Shams S, Louie BH, Seoane JA, Zhou W, Silva TC, Groeneveld C, Wong CK, Cho SW, Satpathy AT, Mumbach MR, Hoadley KA, Robertson AG, Sheffield NC, Felau I, Castro MAA, Berman BP, …
• Integrated Single-Cell Analysis Maps the Continuous Regulatory Landscape of Human Hematopoietic Differentiation.
  Cell 2018 Buenrostro JD, Corces MR, Lareau CA, Wu B, Schep AN, Aryee MJ, Majeti R, Chang HY, Greenleaf WJ
• Transcript-indexed ATAC-seq for precision immune profiling.
  Nature medicine 2018 Satpathy AT, Saligrama N, Buenrostro JD, Wei Y, Wu B, Rubin AJ, Granja JM, Lareau CA, Li R, Qi Y, Parker KR, Mumbach MR, Serratelli WS, Gennert DG, Schep AN, Corces MR, Khodadoust MS, Kim YH, Khavari …
• Preleukemic Hematopoietic Stem Cells in Human Acute Myeloid Leukemia.
  Frontiers in oncology 2017 Corces MR, Chang HY, Majeti R
• Rapid Chromatin Switch in the Direct Reprogramming of Fibroblasts to Neurons.
  Cell reports 2017 Wapinski OL, Lee QY, Chen AC, Li R, Corces MR, Ang CE, Treutlein B, Xiang C, Baubet V, Suchy FP, Sankar V, Sim S, Quake SR, Dahmane N, Wernig M, Chang HY
• Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements.
  Nature genetics 2017 Mumbach MR, Satpathy AT, Boyle EA, Dai C, Gowen BG, Cho SW, Nguyen ML, Rubin AJ, Granja JM, Kazane KR, Wei Y, Nguyen T, Greenside PG, Corces MR, Tycko J, Simeonov DR, Suliman N, Li R, Xu J, Flynn RA, …
• An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues.
  Nature methods 2017 Corces MR, Trevino AE, Hamilton EG, Greenside PG, Sinnott-Armstrong NA, Vesuna S, Satpathy AT, Rubin AJ, Montine KS, Wu B, Kathiria A, Cho SW, Mumbach MR, Carter AC, Kasowski M, Orloff LA, Risca VI, …
• Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist.
  Cancer discovery 2017 McKeown MR, Corces MR, Eaton ML, Fiore C, Lee E, Lopez JT, Chen MW, Smith D, Chan SM, Koenig JL, Austgen K, Guenther MG, Orlando DA, Lovén J, Fritz CC, Majeti R
• Human AML-iPSCs Reacquire Leukemic Properties after Differentiation and Model Clonal Variation of Disease.
  Cell stem cell 2017 Chao MP, Gentles AJ, Chatterjee S, Lan F, Reinisch A, Corces MR, Xavy S, Shen J, Haag D, Chanda S, Sinha R, Morganti RM, Nishimura T, Ameen M, Wu H, Wernig M, Wu JC, Majeti R
• Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution.
  Nature genetics 2016 Corces MR, Buenrostro JD, Wu B, Greenside PG, Chan SM, Koenig JL, Snyder MP, Pritchard JK, Kundaje A, Greenleaf WJ, Majeti R, Chang HY
• A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells.
  Nature medicine 2016 Reinisch A, Thomas D, Corces MR, Zhang X, Gratzinger D, Hong WJ, Schallmoser K, Strunk D, Majeti R
• The three-dimensional cancer genome.
  Current opinion in genetics & development 2016 Corces MR, Corces VG
• Leukemia-Associated Cohesin Mutants Dominantly Enforce Stem Cell Programs and Impair Human Hematopoietic Progenitor Differentiation.
  Cell stem cell 2015 Mazumdar C, Shen Y, Xavy S, Zhao F, Reinisch A, Li R, Corces MR, Flynn RA, Buenrostro JD, Chan SM, Thomas D, Koenig JL, Hong WJ, Chang HY, Majeti R
• Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia.
  Nature medicine 2015 Chan SM, Thomas D, Corces-Zimmerman MR, Xavy S, Rastogi S, Hong WJ, Zhao F, Medeiros BC, Tyvoll DA, Majeti R
• Mutant WT1 is associated with DNA hypermethylation of PRC2 targets in AML and responds to EZH2 inhibition.
  Blood 2014 Sinha S, Thomas D, Yu L, Gentles AJ, Jung N, Corces-Zimmerman MR, Chan SM, Reinisch A, Feinberg AP, Dill DL, Majeti R
• Pre-leukemic evolution of hematopoietic stem cells: the importance of early mutations in leukemogenesis.
  Leukemia 2014 Corces-Zimmerman MR, Majeti R
• Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission.
  Proceedings of the National Academy of Sciences of the United States of America 2014 Corces-Zimmerman MR, Hong WJ, Weissman IL, Medeiros BC, Majeti R
• Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia.
  Science translational medicine 2012 Jan M, Snyder TM, Corces-Zimmerman MR, Vyas P, Weissman IL, Quake SR, Majeti R
• A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression.
  Nature 2011 Wang KC, Yang YW, Liu B, Sanyal A, Corces-Zimmerman R, Chen Y, Lajoie BR, Protacio A, Flynn RA, Gupta RA, Wysocka J, Lei M, Dekker J, Helms JA, Chang HY
• Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age.
  PLoS biology 2010 Kauffman AL, Ashraf JM, Corces-Zimmerman MR, Landis JN, Murphy CT