Ryan Corces

Asst Professor in Residence
Neurology
Research Description: 

The Corces lab melds epigenomics, computational biology, large-scale screens, and single-cell technologies to study neurodegeneration. We make heavy use of primary patient tissue to form hypotheses that can be tested in cellular and organismal model systems. 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.

Primary Thematic Area: 
Neurobiology
Secondary Thematic Area: 
Human Genetics
Research Summary: 
The Corces Lab studies the genetic and epigenetic underpinnings of neurodegenerative diseases using primary human tissue, multi-omic profiling, and large-scale functional genomics assays.

Websites

Publications: 

Single-cell mutational profiling enhances the clinical evaluation of AML MRD.

Blood advances

Ediriwickrema A, Aleshin A, Reiter JG, Corces MR, Köhnke T, Stafford M, Liedtke M, Medeiros BC, Majeti R

Single-cell multiomic analysis identifies regulatory programs in mixed-phenotype acute leukemia.

Nature biotechnology

Granja JM, Klemm S, McGinnis LM, Kathiria AS, Mezger A, Corces MR, Parks B, Gars E, Liedtke M, Zheng GXY, Chang HY, Majeti R, Greenleaf WJ

Circular ecDNA promotes accessible chromatin and high oncogene expression.

Nature

Wu S, Turner KM, Nguyen N, Raviram R, Erb M, Santini J, Luebeck J, Rajkumar U, Diao Y, Li B, Zhang W, Jameson N, Corces MR, Granja JM, Chen X, Coruh C, Abnousi A, Houston J, Ye Z, Hu R, Yu M, Kim H, Law JA, Verhaak RGW, Hu M, Furnari FB, Chang HY, Ren B, Bafna V, Mischel PS

Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion.

Nature biotechnology

Satpathy AT, Granja JM, Yost KE, Qi Y, Meschi F, McDermott GP, Olsen BN, Mumbach MR, Pierce SE, Corces MR, Shah P, Bell JC, Jhutty D, Nemec CM, Wang J, Wang L, Yin Y, Giresi PG, Chang ALS, Zheng GXY, Greenleaf WJ, Chang HY

HiChIRP reveals RNA-associated chromosome conformation.

Nature methods

Mumbach MR, Granja JM, Flynn RA, Roake CM, Satpathy AT, Rubin AJ, Qi Y, Jiang Z, Shams S, Louie BH, Guo JK, Gennert DG, Corces MR, Khavari PA, Atianand MK, Artandi SE, Fitzgerald KA, Greenleaf WJ, Chang HY