About

Thomas Evans is a lecturer at the Cornell Jeb E. Brooks School of Public Policy. His contact email is tevans@cornell.edu. The page does not provide additional details about his research focus, background, or key contributions.

Research topics

• Biology
• Internal medicine
• Medicine
• Genetics
• Virology
• Cell biology
• Immunology
• Pharmacology

Selected publications

• 3D imaging with enhanced transparency, signal-to-background ratios, and antigen detection using HyPer-3D

  Cell Reports Methods · 2026-03-30

  articleOpen access

  -DMSO), a chemical treatment that addresses persistent challenges in 3D imaging of cleared tissues. Imaging across stem cell, zebrafish, and murine model systems demonstrated that HyPer-3D quenches tissue autofluorescence, increases signal-to-background ratios (SBRs) by 30×, potentiates optical clearing capacity by 6×, increases detection of poorly recognized antigens by 4.5×, and enables a 5× increase in fluorescent reporter detection, which are conversely often diminished in 3D imaging. These improvements enhanced multiplex interrogation of highly autofluorescent and fibrous organs, including previously undocumented nephron segments, cardiac conduction system elements, and diffuse spermatogonial stem cells. Optimization for human tissues, which remain among the most difficult to 3D imaging due to autofluorescence and structural density far exceeding those of commonly used animal tissues, yielded a 5× increase in SBRs and enabled multiplex imaging with cellular resolution. Collectively, HyPer-3D provides a robust approach for high-contrast 3D imaging of basic and clinical specimens.

  PublisherDOI

• Restoration of spermatogenesis is dependent on activation of a SPRY4-ERK checkpoint following germline stem cell damage

  Biology of Reproduction · 2026-03-19

  articleSenior author

  Mammalian spermatogonial stem cells (SSCs) sustain male fertility through continuous self-renewal and differentiation, leading to the production of haploid spermatozoa throughout adulthood. However, SSCs are vulnerable to genotoxic drugs, and patients receiving chemotherapy face a high risk of germline instability and infertility. The molecular mechanisms and cellular pathways that choreograph SSC recovery after chemotherapeutic insult remain unknown. Previously, we identified SPRY4 as an ERK-dependent negative feedback regulator of growth factor signaling that is critical for preservation of stem cell activity in cultured mouse SSCs. Here, we demonstrate that following alkylating agent busulfan (BU)-induced injury in adult mice, germline-specific Spry4 gene deletion (Spry4G-KO) reduces stem cell regeneration with an enhanced genotoxic stress response and differentiation with rapidly enhanced nuclear ERK1/2 activity in undifferentiated (Aundiff) spermatogonia (including SSCs). Genes essential for stem cell maintenance, including Id1 and Cxcl12, were dysregulated by loss of Spry4. Furthermore, the MEK1/2 inhibitor PD0325901, but not mTORC1 inhibitor rapamycin, was sufficient to promote spermatogonial proliferation in Spry4G-KO testis 10 days post-BU treatment. Notably, the restoration of both spermatogonia pool and fertility was delayed in adult Spry4G-KO males long-term after injury. In summary, germline-specific deletion of Spry4 results in hyper-activation of the MAPK/ERK pathway in Aundiff spermatogonia, reducing spermatogonial genome integrity, unleashing excessive spermatogenesis after germline damage, and ultimately impairing germline regeneration in adult males. Our study indicates an essential role for SPRY4-ERK signaling as a molecular checkpoint in securing SSC recovery upon chemotherapy drug-induced germline damage, revealing how stem cells normally withstand environmental stress.

  PublisherDOI

• Hypoxia-activated <i>scleraxis a</i> mediates epicardial progenitor differentiation into a unique cardiac perivascular cell type

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-28

  articleOpen access

  Abstract The epicardium is a crucial source of progenitor cells and paracrine signals that support heart development and regeneration. However, the molecular mechanisms that guide epicardial cell fate decisions remain incompletely understood. Here, we identify the transcription factor Scleraxis a (encoded by scxa ) as a key regulator of epicardial progenitor differentiation in zebrafish. Through single-cell transcriptomics, genetic lineage tracing, and cardiac injury models, we show that scxa is transiently induced in activated epicardial progenitor cells (aEPCs) during both heart regeneration and developmental coronary angiogenesis. scxa + epicardial cells primarily give rise to a previously uncharacterized cardiac population of perivascular cells marked by col18a1a , molecularly distinct from classical pericytes and vascular smooth muscle cells. We refer to this population as epicardial-derived perivascular mesenchymal cells (Epi-PMCs). These Epi-PMCs closely associate with coronary vessels and may contribute to vascular stabilization and remodeling, potentially through the anti-angiogenic but vessel-stabilizing activity of endostatin derived from collagen XVIII. Loss of scxa increases coronary vessel density. Mechanistically, we identify hypoxia and Hif1a signaling as upstream regulators of scxa , with systemic hypoxia or Hif factor stabilization robustly inducing scxa expression in the epicardium. Together, these findings uncover a hypoxia-responsive Scxa-Col18a1a axis that drives epicardial differentiation toward a vascular-supportive fate, offering new insight into the regulation of coronary vessel development and the regenerative potential of the epicardium.

  PublisherOA PDFDOI

• Engineering a pacemaker-driven human mini-heart guided by spatial and single cell multi-omics of sinoatrial node development

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-12

  article

  Abstract The human sinoatrial node (SAN) functions as the primary pacemaker of the heart and coordinates the hierarchical electrical activity that drives cardiac contraction. However, experimental systems capable of reconstructing pacemaker-driven cardiac organization in human tissues remain limited. Here we integrate spatial multi-omics of the human fetal SAN with stem-cell engineering to generate pacemaker organoids (“Sinoids”) and assemble them into a pacemaker-driven human mini-heart composed of sinoatrial, atrial and ventricular cardiac modules. High-resolution spatial transcriptomics and single-nucleus multi-omic analyses of human fetal SAN tissues identify regulatory pathways guiding pacemaker lineage specification, which we leverage to engineer human pluripotent stem cell–derived SAN organoids with robust pacemaker identity and electrophysiological activity. When integrated with atrial and ventricular cardioids, Sinoids initiate and coordinate electrical activation across assembled cardiac tissues, establishing directional propagation of electrophysiological signals within structured mini-heart organoids. Combining AI-guided perturbation modeling with functional validation further identifies conserved regulatory pathways controlling pacemaker specification and regionalization, including YAP–TEAD and NRG–ERBB signaling. Together, these results establish a multi-omic–guided strategy for engineering pacemaker tissues and reconstructing cardiac conduction hierarchy in vitro. The pacemaker-driven mini-heart platform provides a modular human cardiac system for studying pacemaker biology, modeling arrhythmia mechanisms and enabling electrophysiological drug discovery.

  PublisherDOI

• GATA6 regulates WNT and BMP programs to pattern precardiac mesoderm during the earliest stages of human cardiogenesis

  eLife · 2025-02-05

  preprintOpen accessSenior author

  Abstract Haploinsufficiency for GATA6 is associated with congenital heart disease (CHD) with variable comorbidity of pancreatic or diaphragm defects, although the etiology of disease is not well understood. Here, we used cardiac directed differentiation from human embryonic stem cells (hESCs) as a platform to study GATA6 function during early cardiogenesis. GATA6 loss-of-function hESCs had a profound impairment in cardiac progenitor cell (CPC) specification and cardiomyocyte (CM) generation due to early defects during the mesendoderm and lateral mesoderm patterning stages. Profiling by RNA-seq and CUT&amp;RUN identified genes of the WNT and BMP programs regulated by GATA6 during early mesoderm patterning. Furthermore, interactome analysis detected GATA6 binding with developmental transcription factors and chromatin remodelers suggesting cooperative regulation of cardiac lineage gene accessibility. We show that modulating WNT and BMP inputs during the first 48 hours of cardiac differentiation is sufficient to partially rescue CPC and CM defects in GATA6 heterozygous and homozygous mutant hESCs. This study provides evidence of the regulatory functions for GATA6 directing human precardiac mesoderm patterning during the earliest stages of cardiogenesis to further our understanding of haploinsufficiency causing CHD and the co-occurrence of cardiac and other organ defects caused by human GATA6 mutations.

  PublisherDOI

• A chemical epigenetic tool to probe site-specific DNA-binding protein complexes

  Proceedings of the National Academy of Sciences · 2025-10-02 · 3 citations

  articleOpen access

  Site-specific DNA binding by proteins is critical for regulating transcriptional activity and cell fate decision. However, identifying proteins bound to specific genomic regions (e.g., promoter or enhancer regions) remains challenging. To address this, we developed a chemical epigenetic tool, named Site-specific noncanonical amino acid-mediated capture of protein (SCOPE), incorporating a photo-crosslinking amino acid into a nuclease-deficient dCas9 mutant. Human pluripotent stem cells (hPSCs) carrying SCOPE enable the capture of proteins bound to, in theory, any genomic location, facilitating the study of the cell context–dependent DNA–protein interactions. Using SCOPE, we identified the OCT4/SOX2/CARHSP1 complex binding to the NANOG promoter to maintain pluripotency in hPSCs. During ectoderm differentiation, ZIC2 acts as a competitive inhibitor, binding the same promoter region to downregulate NANOG expression and promote differentiation. Additionally, SCOPE identified that ZNF8 binds to the distal regulatory region of OCT4 to maintain naïve pluripotency. In summary, SCOPE provides a robust system for uncovering cell context–dependent, site-specific genome regulators, offering valuable insights into gene regulation networks driving cell fate transitions.

  PublisherDOI

• GATA6 Mediates Endoderm and Mesoderm Progenitor Fate Driven by WNT and NODAL Signaling

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-25

  preprintOpen accessSenior authorCorresponding

  SUMMARY During gastrulation, NODAL and WNT signaling drives distinct gene regulatory networks (GRNs) to promote pluripotency exit, specify progenitor fate, and direct lineage differentiation. Here, we employ murine embryonic stem cell directed differentiation toward endoderm and mesoderm lineages to reveal a crucial role of GATA6 during anterior primitive streak-derived progenitor segregation. GATA6 is known to direct by default extra-embryonic endoderm. To promote definitive endoderm fate, GATA6 reinforces the endoderm GRN driven by NODAL while repressing the mesoderm GRN through down-regulation of WNT activity. During progression of mesoderm differentiation, GATA6 induces a switch in the transcriptional output regulated by WNT, promoting lateral mesoderm specification and repression of paraxial mesoderm fate. Thus, this single transcription factor mediates formation of four distinct tissue types, depending on integration of NODAL/WNT activities. Regulation of Eomes and T/Bra expression during anterior primitive streak progression is an essential function of GATA6 during the specification of endoderm or mesoderm fate.

  PublisherOA PDFDOI

• Using hESCs to Probe the Interaction of the Diabetes-Associated Genes CDKAL1 and MT1E

  Cell Reports · 2025-06-01

  erratumOpen access

  As this was article initially published, there are several instances of duplication of immunostaining images presented in Figures 1C,S2A, and S4F.These errors occurred during the final preparation of the figures, when representative images were selected to illustrate the results.To ensure that these errors did not affect the paper's conclusions, the authors verified all raw data used to quantify the results.The results presented in Figure S4F do not affect the quantification results, but the quantification results in Figures 1C andS2A were affected.This quantification was performed again, and the results supported the original conclusions of the paper.The conclusions of this experiment remain unchanged.The corrected versions of the three affected figures appear below.The authors regret the error.

  PublisherOA PDFDOI

• ChemPerturb-seq screen identifies a small molecule cocktail enhancing human beta cell survival after subcutaneous transplantation

  Cell stem cell · 2025-06-24 · 5 citations

  article
  PublisherDOI

• Author response: GATA6 regulates WNT and BMP programs to pattern precardiac mesoderm during the earliest stages of human cardiogenesis

  2025-02-05

  peer-reviewOpen accessSenior author

  Haploinsufficiency for GATA6 is associated with congenital heart disease (CHD) with variable comorbidity of pancreatic or diaphragm defects, although the etiology of disease is not well understood. Here, we used cardiac directed differentiation from human embryonic stem cells (hESCs) as a platform to study GATA6 function during early cardiogenesis. GATA6 loss-of-function hESCs had a profound impairment in cardiac progenitor cell (CPC) specification and cardiomyocyte (CM) generation due to early defects during the mesendoderm and lateral mesoderm patterning stages. Profiling by RNA-seq and CUT&RUN identified genes of the WNT and BMP programs regulated by GATA6 during early mesoderm patterning. Furthermore, interactome analysis detected GATA6 binding with developmental transcription factors and chromatin remodelers suggesting cooperative regulation of cardiac lineage gene accessibility. We show that modulating WNT and BMP inputs during the first 48 hours of cardiac differentiation is sufficient to partially rescue CPC and CM defects in GATA6 heterozygous and homozygous mutant hESCs. This study provides evidence of the regulatory functions for GATA6 directing human precardiac mesoderm patterning during the earliest stages of cardiogenesis to further our understanding of haploinsufficiency causing CHD and the co-occurrence of cardiac and other organ defects caused by human GATA6 mutations.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HL056182

  NIH · $3.9M · 2012

• NIH Grant R01HL064282

  NIH · $3.5M · 2010

• Regulation of Embryonic Erythropoiesis by BMP Signaling

  NIH · $3.2M · 1997–2017

• A molecular pathway controlling cardiomyocyte specification.

  NIH · $2.1M · 2011–2016

• A Gata456 Pipeline of Discovery

  NIH · $5.7M · 2017–2023

Frequent coauthors

• Shuibing Chen

  University of Pennsylvania

  179 shared

• Robert E. Schwartz

  Cornell University

  106 shared

• Yuling Han

  China Jiliang University

  105 shared

• Liuliu Yang

  Shenyang Agricultural University

  99 shared

• Tuo Zhang

  Cornell University

  92 shared

• David D. Ho

  Columbia University

  76 shared

• Jenny Xiang

  Cornell University

  73 shared

• Xiaohua Duan

  73 shared