Primary Mentor:

Xuan Pan, VMD, PhD, DACVIM (Oncology)

Associate Professor, Medical Sciences Department, University of Wisconsin-Madison

Email: [email protected]

Mentor Team:

Emery H. Bresnick, PhD Gary Felsenfeld Professor of Cell and Regenerative Biology Director, Wisconsin Blood Cancer Research Institute

Co-Director, Genetic and Epigenetic Mechanisms Program, Carbone Cancer Center

University of Wisconsin School of Medicine and Public Health Wisconsin Institutes for Medical Research

Email:  [email protected] 

 

Lixin Rui, PhD

Associate Professor, Department of Medicine, University of Wisconsin-Madison, School of Medicine & Public Health

Email:  [email protected]

Description of Potential Research Project(s):

Diffuse large B cell lymphoma (DLBCL) is one of the most common hematological cancers in humans and dogs. The current standard of care for human DLBCL (hDLBCL) and canine DLBCL (cDLBCL) involves cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). However, almost all of canine responders will relapse within one year of the CHOP treatment. Because of the high frequency of relapse and comparable attributes to hDLBCL, cDLBCL offers a powerful comparative model to assess drug resistance mechanisms and develop novel therapeutic strategies to surmount unmet clinical needs. The evolution of multiple tumor subclones during tumor progression generates intratumoral heterogeneity, which plays a role in intrinsic and acquired treatment resistance. Molecular insights into the difference in clinical outcomes of individual patient and the resistance mechanism of CHOP treatment remain largely unknown. We hypothesize that certain genetic mutations confer advantages in lymphoma cell growth, resulting in clonal expansion of the affected cells after CHOP treatment. The project aims to establish tumor-intrinsic and -extrinsic mechanisms that determine CHOP treatment resistance. By integrated analyses of single-cell RNA-seq and whole exome sequencing data, our studies will determine changes in the gene expression profile and mutations in different populations of cells and identify drug-resistance accumulating mutations and pathways. Our study will shed new cellular and molecular insights into the mechanism of CHOP resistance, which provide the mechanistic rationale for the development of targeted therapeutic strategies in both human and canine DLBCLs.

 

Additional Training Opportunities:

The mentoring team involves the collaborative and synergistic efforts of basic and clinical researchers with expertise in canine oncology, human oncology, lymphomagenesis, and genome science. Given Dr. Pan’s expertise in clinical/translational research using in vitro and in vivo tumor models, Dr. Bresnick’s expertise in genome science and hematology, and Dr. Rui’s expertise in cancer genomics and biology,  the collective efforts of the investigators generate a uniquely qualified team to position to train a successful independent researcher in the field of comparative oncology.

 

Contact information:

Xuan Pan, VMD, PhD, DACVIM (Oncology)

Associate Professor, Medical Sciences Department, University of Wisconsin-Madison

Email: [email protected]