Ryan Corces, PhD

Asst Professor in Residence

Primary Thematic Area

M_Neurology

Secondary Thematic Area

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.

Mentorship Development

11/2020 - Optimizing the Efficiency of Your Lab
2/2021 - Three Truths and Three Tries: Facing and Overcoming Critical Social Justice Challenges at the Micro, Mezzo, and Macro Levels
5/2021 - Sharpening your Mentoring Skills (SyMS)
9/2021 - Neuroscience Graduate Program - Disabilities Awareness Training
6/2022 - Career Conversations
10-11/2023 - UCSF Inclusive Mentor/Manager Training

[email protected]

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.

Websites

Corces Lab

Gladstone Institutes - Corces Lab

Publications

CHOIR improves significance-based detection of cell types and states from single-cell data.

Nature genetics

Sant C, Mucke L, Corces MR

Decoding polygenic diseases: advances in noncoding variant prioritization and validation.

Trends in cell biology

Chin IM, Gardell ZA, Corces MR

Chromatin accessibility profiling by ATAC-seq.

Nature protocols

Grandi FC, Modi H, Kampman L, Corces MR

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

Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial DNA.

eLife

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.)

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, Staudt LM, Zenklusen JC, Laird PW, Curtis C, Greenleaf WJ, Chang HY

Integrated Single-Cell Analysis Maps the Continuous Regulatory Landscape of Human Hematopoietic Differentiation.

Cell

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

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 PA, Greenleaf WJ, Davis MM, Chang HY

Preleukemic Hematopoietic Stem Cells in Human Acute Myeloid Leukemia.

Frontiers in oncology

Corces MR, Chang HY, Majeti R

Rapid Chromatin Switch in the Direct Reprogramming of Fibroblasts to Neurons.

Cell reports

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

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, Kundaje A, Khavari PA, Marson A, Corn JE, Quertermous T, Greenleaf WJ, Chang HY

An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues.

Nature methods

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, Kundaje A, Khavari PA, Montine TJ, Greenleaf WJ, Chang HY

Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARa Dependency Targetable by SY-1425, a Potent and Selective RARa Agonist.

Cancer discovery

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

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

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

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

Corces MR, Corces VG

Leukemia-Associated Cohesin Mutants Dominantly Enforce Stem Cell Programs and Impair Human Hematopoietic Progenitor Differentiation.

Cell stem cell

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

Publications

CHOIR improves significance-based detection of cell types and states from single-cell data.

Decoding polygenic diseases: advances in noncoding variant prioritization and validation.

Chromatin accessibility profiling by ATAC-seq.

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

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

Circular ecDNA promotes accessible chromatin and high oncogene expression.

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

HiChIRP reveals RNA-associated chromosome conformation.

Single-cell lineage tracing by endogenous mutations enriched in transposase accessible mitochondrial DNA.

The chromatin accessibility landscape of primary human cancers.

Integrated Single-Cell Analysis Maps the Continuous Regulatory Landscape of Human Hematopoietic Differentiation.

Transcript-indexed ATAC-seq for precision immune profiling.

Preleukemic Hematopoietic Stem Cells in Human Acute Myeloid Leukemia.

Rapid Chromatin Switch in the Direct Reprogramming of Fibroblasts to Neurons.

Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements.

An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues.

Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARa Dependency Targetable by SY-1425, a Potent and Selective RARa Agonist.

Human AML-iPSCs Reacquire Leukemic Properties after Differentiation and Model Clonal Variation of Disease.

Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution.

A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells.

The three-dimensional cancer genome.

Leukemia-Associated Cohesin Mutants Dominantly Enforce Stem Cell Programs and Impair Human Hematopoietic Progenitor Differentiation.

Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia.

Mutant WT1 is associated with DNA hypermethylation of PRC2 targets in AML and responds to EZH2 inhibition.

Pre-leukemic evolution of hematopoietic stem cells: the importance of early mutations in leukemogenesis.

Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission.

Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia.

A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression.

Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age.