Titles and Education

1. VMD-University of Pennsylvania, Philadelphia, PA
   PhD-University of Pennsylvania, Philadelphia, PA
   Rotating Intership-Michigan State University, East Lasing, MI
   Medical Oncology Residency-University of Wisconsin-Madison, Madison, WI

Research

Complementing my translational cancer research, my laboratory investigates the fundamental mechanisms controlling hematopoietic stem cell self-renewal, quiescence, and lineage specification. My laboratory investigates the fundamental molecular mechanisms governing hematopoietic stem cell (HSC) fate decisions, with a focus on chromatin remodeling, epigenetic regulation, and the Polycomb Group protein YY1. We aim to understand how epigenetic mechanisms—particularly Polycomb-mediated regulation and chromatin architecture—control HSC self-renewal, quiescence, lineage specification, and developmental reprogramming in both adult and fetal hematopoiesis.

My laboratory was the first to establish a foundational role for YY1 as a master regulator of HSC biology, demonstrating its essential function in maintaining HSC self-renewal, quiescence, and lineage-specific differentiation. This work pioneered a new understanding of YY1 as a key epigenetic and structural regulator in hematopoiesis and continues to impact the field, guiding subsequent studies of chromatin-mediated control of stem cell fate. Our ongoing studies reveal that YY1 coordinates chromatin architecture through interactions with structural regulators such as CTCF and SMC3, integrates metabolic and lineage-specific programs, and orchestrates lymphoid and myeloid differentiation via Polycomb-dependent and independent mechanisms. Collectively, these studies define fundamental regulators of blood development and disease and position my laboratory at the forefront of molecular and epigenetic regulation of HSC biology.

The vision for my independent research program is to integrate mechanistic stem cell biology with comparative oncology to address fundamental and translational challenges in aging, regeneration, and cancer. By combining discovery-driven science with clinically relevant models, my laboratory seeks to generate broadly applicable biological insights while advancing innovations with direct clinical impact across species. In comparative oncology, we will expand our cfDNA-based cancer detection platform to diagnostic challenging canine cancers with the goal of enabling earlier detection and longitudinal disease monitoring through minimally invasive, low-cost assays. In addition to addressing critical clinical needs, this work provides a powerful framework for defining conserved principles of cfDNA biology and tumor evolution in naturally occurring cancers, strengthening a One Health approach to cancer diagnostics. In parallel, my laboratory will pursue fundamental questions in HSC biology that underlie tissue maintenance, aging, and disease. We will focus on complementary mechanisms that preserve long-term HSC function, including epigenetic regulation of chromatin architecture and stem cell–immune interactions. By defining how regulators such as YY1 organize three-dimensional chromatin to maintain stem cell identity and how immune checkpoint pathways shape regenerative capacity, our work will connect intrinsic stem cell programs with extrinsic immune control. Together, this integrated research vision establishes a bidirectional pipeline in which clinical challenges inform mechanistic discovery and fundamental insights guide translational innovation.

Responsibilities

Comparative Biomedical Sciences (CBS) Graduate Program 

Cellular & Molecular Biology (CMB) Graduate Program 

Cancer Biology Graduate Program

Clinical Interests

My translational research program focuses on innovative cancer detection and treatment strategies in comparative oncology, with an emphasis on precision oncology using naturally occurring canine cancers as comparative models. This program represents a unique integration of veterinary clinical insight and molecular innovation, with projects conducted through a collaborative effort between the UW School of Veterinary Medicine (SVM) and the Center for Precision Medicine. A key innovation from this program is the development of a blood-based cancer detection platform leveraging cell-free DNA (cfDNA) fragmentation patterns combined with machine learning. This mutation-agnostic, noninvasive approach represents a fundamentally new diagnostic strategy and has led to WARF-filed intellectual property and active clinical implementation at University of Wisconsin Veterinary Care. This work demonstrates a clear pathway from laboratory discovery to patient-facing application. More broadly, this research exemplifies a bidirectional translational model, in which clinically driven questions in veterinary oncology generate mechanistic insights directly applicable to human cancer, while laboratory discoveries inform clinical practice in both species. These outcomes highlight the impact, originality, and translational relevance of my research program and its contribution to advancing One Health–oriented cancer diagnostics.

In parallel with cancer detection, my laboratory is advancing novel targeted therapies for canine cancers. Naturally occurring cancers in pet dogs closely mirror human malignancies with respect to histopathology, molecular drivers, tumor genetics, and therapeutic response. We demonstrated clinical benefit of the tyrosine kinase inhibitor toceranib in canine anal sac adenocarcinoma, providing the first evidence-based support for its use in this disease and offering practical guidance for therapeutic decision-making in veterinary oncology. This work has directly impacted clinical practice by informing treatment selection and expectations for outcomes in affected dogs. In addition, we identified the NEDD8-activating enzyme inhibitor pevonedistat as a targeted therapeutic for canine melanoma through induction of DNA replication stress and cellular senescence.

Graduate Training

Cell & Molecular Biology

Veterinary Medical Oncology

Recent Publications

1. Wang, YG., and Pan. X.  YY1 in Hematopoietic Stem Cells: Epigenetic Regulation, Chromatin Architecture, and Aging.  Current Opinion in Hematology. 2026 April 7 . doi: 10.1097/MOH.0000000000000925. PMID: 42047481
2. Favaro, P., Wang, YG., McDonald, B., Wang, TS., Ambewadkar, S., Cheng, HV., Marcinak, C., *#Pan, X.,Murtaza, M. Comparative analysis of fragmentation patterns in canine and human plasma DNA. Cancer Research Communications. 2026 Jan 16. doi: 10.1158/2767-9764.CRC-25-0373. (#co-corresponding author)
3. Saka, Sp., Lu, Zp., Wang, YG., Liu, P., Singh, Dp., Lee, JG., Palii, G., Alvarez, TI., Assumpção, AG., You, X, Brand, M., Zhang, J., Atchison, M., and *Pan, X.  Chromatin factor YY1 controls fetal hematopoietic stem cell migration and engraftment in mice.  J Clin Invest. 2025 Jul 29:e188140. doi: 10.1172/JCI188140. PMID: 40762953
4. Srinivasan L, Pan X, Atchison ML. Transient requirements of YY1 expression for PcG transcriptional repression and phenotypic rescue. J Cell Biochem. 2005 Nov 1;96(4):689-99. doi: 10.1002/jcb.20562. PMID: 16052488.
5. Deng, C., Bridenstine, A., Song, A., Ceplina, R., Ostheimer, C., Hahn, M., Scarlett, C., Saka, SP., Pan, X., Tamplin, O., GABA produced by multiple bone marrow cell types regulates hematopoietic stem and progenitor cells. Stem Cell Reports. 2025 Nov 11;20(11):102677. doi:10.1016/j.stemcr.2025.102677
6. Lu Z, Hong CC, Kong G, Assumpção ALFV, Ong IM, Bresnick EH, Zhang J, Pan X. Polycomb Group Protein YY1 Is an Essential Regulator of Hematopoietic Stem Cell Quiescence. Cell Rep. 2018 Feb 6;22(6):1545-1559. PubMed PMID: 29425509.
7. Assumpção AL, Fu G, Singh D, Lu Z, Kuehnl AM, Welch R, Ong IM, Wen R and Pan X. A Lineage-specific Requirement for YY1 Polycomb Group Protein Function in Early T cell development. Development. 2021 Mar 25;dev.197319.doi: 10.1242/dev.197319.
8. Wood EA, Lu Z, Jia S, Assumpção ALFV, Hesteren MV, Huelsmeyer MK, Vail DM, Pan X. Pevonedistat targeted therapy inhibits canine melanoma cell growth through induction of DNA re-replication and senescence. Vet Comp Oncol. 2019 https://doi.org/10.1111/vco.12546
9. Assumpção, A., Lu, Z., Marlowe, K., Shaffer, K. and Pan, X., Targeting NEDD8-activating enzyme is a new approach to treat canine diffuse large B cell lymphoma. Vet Comp Oncol. 2018 July DOI: 10.1111/vco.12428

10. Assumpção ALFV, Jark PC, Hong CC, Lu Z, Ruetten HM, Heaton CM, Pinkerton ME, Pan X. STAT3 Expression and Activity are Up-Regulated in Diffuse Large B Cell Lymphoma of Dogs. J Vet Intern Med. 2018 Jan;32(1):361-369. PubMed PMID: 29119628; PubMed Central PMCID: PMC5787155. 

11.  Lu Z, Hong CC, Jark PC, Assumpção ALFV, Bollig N, Kong G, Pan X. JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation. J Vet Intern Med. 2017 Nov;31(6):1804-1815. PubMed PMID: 28960447; PubMed Central PMCID: PMC5697192. 

12. ​​​​​​Pan X, Tsimbas K, Kurzman ID, Vail DM. Safety evaluation of combination CCNU and continuous toceranib phosphate (Palladia(®) ) in tumour-bearing dogs: a phase I dose-finding study. Vet Comp Oncol. 2016 Jun;14(2):202-9. PubMed PMID: 24735385.
13. Pan, X., Papsani, M., Hao, Y., Calamito, M., Wei, F., Quinn, W., Wang, JW., Shi, Y., Allman, D., Cancro, M. and Atchison, M.L.,  YY1 controls Igk repertoire and B-cell development, and localizes with condensin on the Igk Locus.  EMBO J., doi: 10.1038/emboj.2013.66 (2013).
14. Pan, X., Jones, M., Jiang, J., Yu, D.N., Pear, W., Maillard, I. and Atchison, M.L., Increased Expression of PcG Protein YY1 Negatively Regulates B Cell Development While Allowing Accumulation of Myeloid Cells and LT-HSC Cells.   PLoS One. 7(1):e30656 (2012)
    
15. Basu, A., Hodawadekar, S., Andrews, O., Knox, A., Pan, X., Wilkinson, F. and Atchison, M.L., YY1 PcG Function as a Potential Cancer Therapeutic Target.  Forum Immunopath. Dis. Ther. 1: 31-50 (2010).