Precision Medicine Interest Group Seminars

Syed Nabeel Zafar MBBS MPH is an Assistant Professor of Surgery within the division of Surgical Oncology at the University of Wisconsin, Madison and is visiting faculty within the department of Surgery at Aga Khan University. Dr. Zafar completed his medical training from the Aga Khan University, an MPH from the Harvard T. H. Chan School of Public Health followed by a general surgery residency at Howard University, and fellowships in Advanced GI Minimally Invasive Surgery at the University of Maryland, and Complex General Surgical Oncology at the MD Anderson Cancer Center.  Dr Zafar is certified by the American Board of Surgery and the American Board of Medical Quality. His clinical practice is in gastrointestinal cancers including gastric, hepatopancreaticobiliary, and peritoneal surface malignancies with a focus on minimally invasive approaches.

Dr. Zafar conducts health services research and analyzes large datasets to study outcomes after cancer surgery, as well as disparities in outcomes after surgical care. Dr. Zafar has published over 109 scientific articles, 7 book chapters and has presented his work in over 50 local, national and international meetings. His work is funded by intramural awards as well extramural- NIH awards from the NCI. He current work aims as prediction modeling for outcomes after surgery for pancreas cancer.

“Predictive modeling Outcomes after Pancreatic Cancer Surgery”

The goal of the Bailey Laboratory is to make meaningful contributions to the fight against global infectious diseases. This includes using patient data and patient specimens to study the pathogenesis of infectious diseases in humans; developing new animal models to explore the pathophysiology of viral diseases; using animal models to evaluate new therapeutics and vaccines; utilizing in vitro technologies and high-throughput screens to investigate molecular mechanisms governing host-pathogen interactions; and developing new tools for the diagnosis of emerging infectious diseases. Current projects focus on a variety of areas including the mechanistic basis of hemorrhage in viral hemorrhagic fever; host factors governing yellow fever virus tropism and pathogenesis; virus discovery; and characterization of the immune evasion mechanisms of several RNA viruses. Providing a culture of curiosity, creativity, respect, and rigor in which the next generation of scientists can maximize their learning potential is also a critical component of the Bailey Lab’s mission.

“Precision pandemic preparedness: counteracting animal viruses before they emerge”

Dr. Peter Lewis is an Associate Professor in the Department of Biomolecular Chemistry. His research seeks to define the biochemical mechanisms involved in the establishment and maintenance of silent chromatin, also known as heterochromatin.

The goal of the Lewis lab is to understand the biochemical mechanisms involved in establishing and maintaining silent chromatin, also known as heterochromatin. To maintain cellular identity, it is essential to keep genes specific to certain lineages silent, and failure to do so can lead to developmental defects or promote tumor growth. Their research employs various techniques, including highly purified biochemical assays, proteomic and genomic analyses, and genetic screens, to study these processes.

Dr. Morris is an associate professor in the Department of Human Oncology and a physician-scientist with a clinical focus on the treatment of patients with sarcomas and melanoma using radiation therapy. His translational research lab is focused on developing novel approaches to improving the treatment of cancer patients by integrating radiation therapy and immunotherapies to achieve curative outcomes.

“Priming and propagating anti-tumor immunity using radiation therapy”

In this talk, Dr. Tiwari will focus on her lab’s recent efforts in developing machine learning techniques to capture insights into the underlying tumor biology as observed across non-invasive imaging, histopathology, and omics data. She will focus on applications of this work for predicting disease outcome, recurrence, progression and response to therapy specifically in the context of brain tumors. She will also discuss current efforts in developing new image-based features for post-treatment evaluation and predicting response to chemo-radiation treatment. Dr. Tiwari will conclude her talk with a discussion of some of the translational aspects of her work from a clinical perspective.

The Bresnick group conducts basic and translational research on genomics/epigenomics and normal and malignant hematopoiesis. They have discovered GATA2 enhancers and mechanisms that are essential for hematopoiesis and embryonic development, and their disruption generates a predisposition to develop myelodysplastic syndromes and acute myeloid leukemia. Studies on GATA2, DDX41 and other critical determinants of hematopoiesis have unveiled paradigms to explain hematopoietic stem cell generation, progenitor fate decisions, and erythrocyte development as well as clinical genetic diagnostic strategies.

“From Human Genetics to Stem Cell and Blood Cancer Mechanisms and Applications”

After receiving a PhD from the University of Massachusetts Amherst and doing a post-doctoral fellowship at the NY University School of Medicine, Dr. Mathew’s research and academic service focus has been on development of technological devices, informatics platforms, data analytics and decision support for improving wellness, disease prevention, early diagnosis, and efficient disease management. She has also led development of phenotype registries with metadata and standard vocabulary from EHR data. Most recently she served as Chief Research Informatics Officer at the University of Massachusetts Medical School. Dr. Mathew became associate dean for informatics and information technology for the School of Medicine and Public Health in October 2021.

 “The Wisconsin Real World Data Collaborative: A project to integrate RWD and improve access to data for RWE at SMPH”

Dr. Savage is certified by the American Board of Surgery in General Surgery and Surgical Critical Care. Her clinical practice focuses on care of the acute injured patient, the management of emergent general surgical diseases and providing critical care in the Intensive Care Unit setting. Dr. Savage is nationally recognized and serves on multiple committees for the American Association for the Surgery of Trauma, the Western Trauma Association, the Eastern Association for the Surgery of Trauma and the American Board of Surgery. Dr. Savage’s research interests focus on massive hemorrhage and the interaction between abnormal clot formation and inflammation following injury. Dr. Savage is also well-published in research surrounding Emergency General Surgery grading systems and management.

“Interplay of Coagulation and Inflammation following Major Injury”

Dr. Lixin Rui is a faculty member in the Division of Hematology, Medical Oncology and Palliative Care within the Department of Medicine. He is a lecturer and trainer in several University of Wisconsin School of Medicine and Public Health basic science courses and graduate programs. A former UW Institute for Clinical and Translational Research (ICTR) KL2 scholar, Dr. Rui has an active lymphoma biology research program. He is a member of the American Society of Hematology and the American Association for Cancer Research.

Dr. Rui’s research focuses on lymphoma biology, with an emphasis on JAK-STAT signaling in lymphomagenesis. Deregulation of this pathway contributes to pathogenesis of Hodgkin lymphoma and Non-Hodgkin lymphoma, including aggressive diffuse large B-cell lymphoma. Dr. Rui’s research aims to identify JAK and its downstream molecular targets for therapeutic applications to these cancers. His research interests also include investigation of the F-box protein FBXO10, which he has recently characterized as a potential tumor suppressor.

Dr. Kelly’s primary clinical practice includes the treatment of upper gastrointestinal malignancies, including gastric, pancreatic, and hepatobiliary cancers, as well as peritoneal surface malignancy, melanoma, and sarcoma. She is particularly interested in developing minimally invasive techniques for cancer surgery. Dr. Kelly’s primary clinical and research interest is gastric cancer. She is among the highest-volume gastric cancer surgeons in the country with over 10 year of experience, and has pioneered minimally-invasive surgical techniques for gastrectomy with comprehensive lymph node removal. Dr. Kelly also performs some operations with an open technique when necessary, and can perform additional procedures to treat liver cysts, chronic pancreatitis, and gallbladder disease. Dr. Kelly is board-certified in Complex General Surgical Oncology and General Surgery.

Dr. Lu received his Bachelor’s at Tsinghua University (Mathematics, 2012) and Ph.D. at Yale University (Biostatistics, 2017). He is currently an Assistant Professor in the Department of Biostatistics and Medical Informatics at UW-Madison. The Lu Lab develops and employs statistical methods to identify and interpret genetic associations for human complex traits. In particular, areas of expertise in the Lu Lab include genome-wide association study, non-coding genome annotation, genetic correlation estimation, polygenic risk prediction, and gene-environment interaction.

“Optimizing and benchmarking polygenic risk score with GWAS summary data”

Jessica obtained her bachelors (Genetics, 2009) and doctorate (Cancer Biology, 2014) at the University of Wisconsin-Madison. She then completed two postdoctoral fellowships at Arizona State University and The Translational Genomics Research Institute (TGen). Jessica was awarded an NCI K99/R00 in 2019 to focus her studies on the role of super-enhancers in high-grade serous ovarian carcinomas. She joined the University of Wisconsin-Madison faculty in 2021, where she will leverage her experience in translational biology, genomics, and epigenetics.

The Lang Lab employs genomics technologies and translational models to determine the role of somatic mutation to epigenetic modifiers in the development and therapeutic vulnerabilities of ovarian cancers.

“Therapeutic vulnerabilities in ovarian cancers and implications of platinum treatment”

Mark Craven is a professor in the Department of Biostatistics and Medical Informatics at the University of Wisconsin, and an affiliate faculty member in the Department of Computer Sciences. The focus of his research program is to develop and apply machine-learning methods to infer models of networks of interactions among genes, proteins, clinical variables, environmental factors, and phenotypes of interest. He leads the Biostatistics and Bioinformatics Core of the Children’s Respiratory and Environmental Workgroup (CREW), which is the pediatric asthma project in the NIH Environmental Influences on Child Health Outcome (ECHO) program. He is also the Director of the NIH/NLM-funded Computation and Informatics in Biology and Medicine (CIBM) Training Program, and a member of the Center for Genomic Science Innovation, the Institute for Clinical and Translational Research, and the Carbone Cancer Center. He currently serves on the National Advisory Council for Human Genome Research (NHGRI Council) and as the co-chair of the NHGRI Genomic Data Science Working Group.

A Perspective on Recent Trends in Data Science for Human Genomics

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Dr. Jane Churpek is an Assistant Professor in the Division of Hematology, Medical Oncology, and Palliative Care at The University of Wisconsin-Madison. She is Board Certified in Internal Medicine, Hematology, and Oncology. In her clinical practice, she cares for adults with low blood counts due to acquired and inherited causes, including clonal hematopoiesis and inherited bone marrow failure syndromes, and performs diagnosis and management of diverse predisposition syndromes such as familial leukemia, Li Fraumeni syndrome, BAP1 syndrome, etc. She runs a translational research program aimed at defining the inherited basis of cancer and bone marrow disorders, especially among understudied tumors and blood disorders. Her goal is to improve diagnosis, early detection, treatment and, ultimately, prevention of morbidity and mortality for patients with these disorders. Dr. Churpek has contributed to the understanding of several novel hereditary blood cancer predisposition syndromes and the role of inherited predisposition in exposure associated cancers such as therapy-related leukemia and mesothelioma.

Inherited Cancer Susceptibility: Windows into Etiology and Biology

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Dr. Hess is an Assistant Professor in the Department of Biomolecular Chemistry and the Center of Human Genomics and Precision Medicine. Before arriving at UW-Madison, Dr. Hess received his undergraduate degree in chemistry and physics from Harvard University and then his PhD in Biophysics, also from Harvard University while studying with Angela Belcher from MIT. For his thesis work, he established a labeling method for M13 bacteriophage to generate higher-order nano-material scaffolds and led a project to employ high-throughput sequencing for improved peptide phage display.

His interests lie within building new functional genomics tools to dissect the link between genotype and phenotype. Using these tools, he will investigate mechanisms of DNA repair, therapeutic response, and pathogens, which will enhance the treatment and diagnosis of patients.

High-throughput functional genomics for studying fundamental biology and improving human health

Dr. Lo Sardo was born and raised in Italy. She graduated from college at the University of Milan, in Pharmaceutical Biotechnology. She then continued and earned her PhD in Biotechnology at the University of Milan, working with Dr. Elena Cattaneo in the laboratory of Stem Cell Biology and Pharmacology of Neurodegenerative Diseases. During her training, she developed extensive expertise in generating, culturing, differentiating, and manipulating mouse and human pluripotent stem cells (PSCs). During her PhD, she focused on rare genetic variants and neurological diseases. In particular, she studied the gene product of Huntington Disease, huntingtin, during early neuronal development. This work described for the first time an unknown function of huntingtin protein in regulating cell adhesion in the developing nervous system. Moreover, these studies elucidated how huntingtin evolved in different species to acquire specific neural functions only in organisms with complex nervous system.

Next, Dr. Lo Sardo moved to US for her postdoctoral studies and joined The Scripps Research Institute in La Jolla, California. Her work in Dr. Kristin Baldwin’s laboratory focused on understanding genomic variations and cell fate determination. Her postdoctoral research focused on human-specific functional genomics, using reprogramming technology and iPSC differentiation assays. She did seminal work on the functional annotation of cardiovascular disease genetic risk factors. In particular, she studied the function of the 9p21 cardiovascular disease risk locus, the most common and influential genetic risk factor for coronary artery disease (CAD), the first cause of death worldwide. By using iPSC-isogenic lines and precision large-scale genome editing, her studies uncovered new gene networks involved in the pathogenesis of CAD, highlighting the major role of Vascular Smooth Muscle Cells (VSMCs) as a key cellular type. Dr. Lo Sardo’s contribution to these discoveries was recognized by high-impact first-author publications. Dr. Lo Sardo also implemented public resources in the Stem Cell field by generating a large collection of iPSCs from donors at an advanced age, deposited at WiCell and, as part of training effort of the American Society for Neuroscience, providing protocols used to consolidate and standardize the use of stem cells in neuroscience.

Dr. Lo Sardo joined UW-Madison in September 2020. Her lab combines the use of pluripotent stem cells and functional genomics to understand how common genetic variants among individuals, including those in non-coding portions of the genome, contribute to altering cell physiology, cell state, and fate commitment. Emphasis is posed on understanding non-coding risk factors, cell-type vulnerability, as well as ethnicity-based vulnerability to human diseases. Using multidisciplinary approaches, including pluripotent stem cell differentiation, genome editing, transcriptomics, and imaging, her lab aims to identify new molecular mechanisms triggering cardiovascular disease and cancer.

Deciphering the non-coding genome with iPSCs and genome editing

Wendy Chung, M.D., Ph.D. is a clinical and molecular geneticist and the Kennedy Family Professor of Pediatrics and Medicine and Director of Clinical Genetics.  She received her B.A. in biochemistry and economics from Cornell University, her M.D. from Cornell University Medical College, and her Ph.D. from The Rockefeller University in genetics.  Dr. Chung directs NIH funded research programs in human genetics of pulmonary hypertension, autism, birth defects including congenital diaphragmatic hernia and congenital heart disease.  She is a national leader in the ethical, legal, and social implications of genomics.  She leads the Precision Medicine Resource in the Irving Institute At Columbia University.  She has authored over 500 peer reviewed papers and 75 reviews and chapters in medical texts.  She was the recipient of the Medical Achievement Award from Bonei Olam, the NY Academy of Medicine Medal for Distinguished Contributions in Biomedical Science, the Rare Impact Award from the National Organization of Rare Disorders, and is a member of the National Academy of Medicine and the American Academy of Physicians.  Dr. Chung enjoys the challenges of genetics as a rapidly changing field of medicine and strives to facilitate the integration of genetic medicine into all areas of health care in a medically, scientifically, and ethically sound, accessible, and cost effective manner.

Genomic Medicine: Opportunities and Challenges