Message from the Vice Chair for Research
August brings us Research Highlights from the DOM’s largest Division, Hematology and Oncology. Leading this division is Dr. Lisa Carey, who has an international reputation for her expertise and research in breast cancer. Hem/Onc’s goal is not only to provide the best cancer care in North Carolina (or anywhere) but to lead research into causes, biology, treatment, and outcomes. Hem/Onc has collaborations with faculty throughout UNC, connecting significantly via the UNC Lineberger Comprehensive Cancer Center, which is supported by the National Cancer Institute, and the McAllister Heart Institute. The research in this broad organization begins with molecules, expands out to animal models, includes patient trials, considers socioeconomic and social aspects of cancer, and aims toward the sky. An amazingly diverse and impressive group of scientists are part of this organization, and I am proud to highlight five of the great physicians and scientists from the team.
Janet Rubin, MD
Vice Chair for Research
Satish Gopal, MD, MPH
Dr. Gopal went to medical school at Duke University, and trained in medicine-pediatrics at the University of Michigan. He completed medical oncology and infectious diseases fellowships at the University of North Carolina and is board certified in both disciplines.
He lived in Tanzania from 2007 until 2009 where he provided HIV clinical care after his residency before pursuing combined fellowship training. After fellowship, he moved with his wife and two daughters to Malawi where he has lived since 2012, and where he is the only medical oncologist in a country of 17 million people. In Malawi, Dr. Gopal serves as the Cancer Program Director at UNC Project-Malawi, a longstanding clinical research collaboration between the University of North Carolina and Malawi Ministry of of Health. In this capacity, he supports involvement of the site in several NIH clinical trial networks: as an AIDS Malignancy Consortium investigator, a Cancer Working Group member for the Centers for AIDS Research Network of Integrated Clinical Systems network (CNICS), and a Cancer Working Group member for the International Epidemiologic Databases to Evaluate AIDS (IeDEA) network, an NIH-funded consortium of HIV cohorts worldwide.
Dr. Gopal is an Honorary Senior Lecturer at the University of Malawi College of Medicine. He is PI for a large multicenter HIV-associated lymphoma cohort study in CNICS, and PI for the Kamuzu Central Hospital Lymphoma Study, one of the first large prospective clinical cohorts of lymphoproliferative disorders in sub-Saharan Africa, with embedded virologic and genomic substudies. He is PI for the NIH U54 Malawi Cancer Consortium, a broad national effort focused on developing capacity for HIV-associated cancer research, and conducting high-impact research for Kaposi sarcoma and lymphoma in Malawi. He is also PI for the recently funded NIH P20 effort to establish a multilateral center for research excellence in Malawi focused on non-communicable diseases, including cancer.
His principal scientific work to date has focused on clinical and epidemiologic studies of HIV-associated malignancies in resource-limited settings, as well as developing resource-appropriate strategize to optimize prevention, diagnosis, and treatment of commonly occurring cancers in sub-Sahara. These latter efforts involve a multidisciplinary team of collaborators from the population, basic, and clinical sciences across the University of North Carolina campus. Key outputs of the Malawi cancer program to date have included building novel real-time telepathology diagnostic infrastructure in Lilongwe, developing among the first detailed longitudinal outcomes data for children and adults receiving curative-intent lymphoma treatment in sub-Saharan Africa, and providing among the first detailed clinical descriptions of HIV-associated multicentric Castleman disease from sub-Saharan Africa. He also leads Malawi participation in NCI cancer clinical trial networks in sub-Saharan Africa. Already well-published, Dr. Gopal is already influential; his editorial in April 2016 in the New England Journal of Medicine exhorted the cancer research community and policymakers to address global disparities in cancer care.
Although he is based full-time in Malawi, Dr. Gopal returns to Chapel Hill each year to attend on the inpatient teaching services at the North Carolina Cancer Hospital. He also provides research mentorship to a growing team of US and Malawi junior investigators with global cancer career interests.
Carey Anders, MD
Dr. Anders is a clinician-scientist and an Associate Professor of Medicine within the Department of Medical Oncology and an active member in the UNC Lineberger Comprehensive Cancer Center and the UNC Breast Center. Her clinical interests include the care of patients with all stages of breast cancer, particularly those who are young at diagnosis and those with brain metastases. During her fellowship at Duke University, she became acutely aware of the clinical challenge of brain metastases arising from breast cancer and the lack of systemic therapeutics to treat this disease. While at UNC, she has focused her translational research program on the biology and treatment of breast cancer brain metastases, which include lesions arising from aggressive triple negative breast cancer.
Dr. Anders’ research program spans the bench to the bedside. From a laboratory perspective, her research has focused on unraveling the biologic complexity of and impact of the immune system on breast cancer brain metastases. She and her research team have developed intracranial models of triple negative breast cancer brain metastases which provide the platform to test novel anti-cancer drugs, including novel delivery platforms such as liposomes and nanoparticles. In parallel, she and her team were recently awarded an Advanced Clinical Research Award (ACRA) from the American Society of Clinical Oncology (ASCO) to perform next generation RNA and DNA sequencing on breast cancer brain metastasis tissues and matched primary breast tumors to better understand the genetic underpinnings of the metastatic process with the goal of discovering novel and rationale targets to prevent and treat brain metastases.
In parallel to her preclinical efforts, Dr. Anders co-founded the UNC multidisciplinary brain metastasis clinic, the first of its kind in the United States, with her colleagues in Radiation Oncology and Neurosurgery. Within this clinic, her team sees patients with breast cancer brain metastases to offer coordinated, multidisciplinary care. Dr. Anders is the principal investigator of multiple clinical trials for promising, brain-permeable anti-cancer agents including inhibitors of DNA damage repair (PARP) and cell cycling (CDK4/6 inhibitors). In addition, she leads trials in the delivery of nanoparticle and carrier-mediated anti-cancer agents to enhance brain delivery. She remains very active in several clinical trial consortiums including the Translational Breast Cancer Research Consortium (TBCRC) and the Alliance. In addition to running her own clinical and research programs, she enjoys mentoring students at all levels of training in her laboratory and clinic. Finally, while not at work, Dr. Anders enjoys spending time and traveling with her young daughter and supportive husband. She remains an avid runner.
Rafal Pawlinski, PhD
Dr. Pawlinski earned his graduate degree at the Jagiellonian University in Krakow, Poland and obtained postdoctoral training at the Scripps Research Institute (La Jolla, California). In 2008, he joined the Division of Hematology and Oncology to continue his research in the field of thrombosis, hemostasis and inflammation. Shortly thereafter he was awarded the Kenneth M. Brinkhous Young Investigator Prize in Thrombosis from the American Heart Association for his work on the crosstalk between coagulation and inflammation, and identifying the cellular sources of tissue factor that contribute to the activation of coagulation during sepsis.
Recently, a significant part of Dr. Pawlinski’s research effort has focused on sickle cell disease (SCD), the most prevalent genetic disorder worldwide. SCD is a hematologic disorder caused by a single nucleotide mutation in the β-globin gene, with hemolytic anemia and vaso-occlusive crises being the primary clinical manifestations of the disease. It is also associated with chronic vascular inflammation and activation of coagulation. His laboratory made the exciting discovery that inhibition of tissue factor, the primary cellular initiator of coagulation, not only reduces coagulation but also mitigates vascular inflammation in mouse models of SCD. This observation formed the scientific foundation for $8.2-million, multiple investigator grant from the NIH-NHLBI to UNC to study the role of coagulation in the pathology of SCD. The proposal includes a clinical trial investigating the effect of the novel Factor Xa inhibitor Rivaroxaban. The overall goal of the project is to design anticoagulant therapies that prevent vascular inflammation and end organ damage in SCD without increasing bleeding risk. Additional studies explore the effects of SCD on properties and dynamics of clot formation and studies to understand the mechanism of silent stroke in sickle cell patients.
Dr. Pawlinski and his group are also interested in the role of coagulation proteases in the pathology of cardiovascular and neurological diseases. In addition to their role in hemostasis and thrombosis, coagulation proteases induce various cellular responses via proteolytical cleavage of protease activated receptors (PARs). His lab is interested in the molecular mechanism by which PARs contribute to the pathophysiology of myocardial infarction-induced heart remodeling, stroke and multiple sclerosis.
In a parallel universe he enjoys “assimilating” science fiction in many forms, watching ice hockey (two favorite teams: Anaheim Ducks and Carolina Hurricanes), training for his first half-marathon (a daunting task!), and spending time with his wife and two children.
Ethan Basch, MD, MSc
Dr. Basch is a medical oncologist and outcomes researcher who has championed bringing the patient’s voice into cancer clinical research, practice, and quality assessment. His research group has developed and tested patient questionnaire systems that are now standard in cancer drug development, and they are testing electronic ‘patient-reported outcomes’ nationally in oncology practices to improve quality of care. His recently published randomized controlled trial found that administering simple symptom questionnaires during chemotherapy improves patients’ quality of life and survival, and reduces emergency room visits. His group developed the standard system for patient reporting of adverse events in cancer trials for the National Cancer Institute, called the "PRO-CTCAE", which is now widely recommended by the FDA.
Outside UNC, Dr Basch leads and participates in various national committees, including the National Cancer Institute’s Board of Scientific Advisors, PCORI’s Methodology Committee, and as an Associate Editor for JAMA. At UNC, he leads the Cancer Outcomes Research Program, which is supported by Lineberger Comprehensive Cancer Center and involves faculty members from across the university focused on quality, access, financing, and patient-centeredness of cancer care – and hosts a popular southern breakfast and seminar every Tuesday during the semester serving biscuits and gravy, grits, eggs and other fare, as well as national speakers on cancer health services research. Dr. Basch holds dual appointments in the Department of Medicine and the Department of Health Policy and Management in the School of Public Health, and co-leads the Cancer Prevention and Control Program.
Dr. Basch is funded by the National Cancer Institute, Department of Defense, PCORI, AHRQ, and multiple foundations. He recently received a new $5.5m PCORI award to study patient-reported outcomes in oncology practice across the US which has just kicked off. This project is in collaboration with the major oncology specialty societies, quality assessment organizations, and patient advocacy groups. This is an exciting project that is intended to lead to wide implementation of more patient-centered quality metrics in clinical practice – the concept being that nausea or pain control following chemotherapy is an important quality metric of interest to patients, clinicians, and payers.
Clinically, Dr. Basch focuses largely on prostate cancer. Caring for this population has been gratifying and informs much of his research. He has led multiple national guidelines and consensus panels on prostate cancer over the years and has chaired registries for this disease. His group defined the definitive approach to pain assessment for drug development, which is now widely used in industry for prostate cancer trials.
Dr. Basch came to UNC five years ago with his wife Joy and two children from New York, where he was on faculty at Memorial Sloan Kettering Cancer Center. Prior to that, he received his MD and MSc in epidemiology from Harvard, an MPhil in 20th century literature from Oxford, did his residency in internal medicine at Mass General, and oncology fellowship at Sloan Kettering. They love living in Chapel Hill and transitioned seamlessly from a NY apartment to a farm house on a country road next to cows. He plays jazz bass and can be heard from time to time playing around town, including at the Eddy Pub in Saxapahaw, G2B Gastropub in Durham, and on the Weaver Street lawn for occasional Sunday brunches.
Jonathan Serody, MD
Dr. Serody is the Associate Director for Translational Science at the Lineberger Comprehensive Cancer Center, co-leader of the Immunology program for the Cancer Center, and a Vice-Chief of the Division of Hematology and Medical Oncology. Dr. Serody and his laboratory have been working for the past 2 decades to enhance our knowledge of transplantation and tumor immunology and to use this information to improve the outcome of patients undergoing bone marrow transplantation or being treated for malignant disease. The Serody laboratory and their collaborators at the University of Minnesota were the first to use mice transgenic for the enhanced green fluorescent protein to track where donor immune cells are activated after bone marrow transplantation. This work demonstrated that T lymphocytes engraft in lymphoid tissue and has paved the way for novel approaches to prevent acute GVHD by preventing the migration of lymphocytes into and out of lymphoid tissue. Additionally, the Serody laboratory was the first to demonstrate a critical role for proteins that control T cell migration in the biology of acute GvHD. This work has led to the development of maraviroc, a CCR5 inhibitor, as an approach to prevent GvHD and the identification of chemokine proteins such as CXCL9 and CXCL10 as biomarkers for the disease. The Serody laboratory is currently working on identifying a unique role for subsets of innate lymphoid cells in the biology of lower GI tract GvHD and developing cellular therapies to treat patients with lower GI tract GvHD who are non-responsive to conventional therapy.
In the past 5 years, the Serody laboratory has focused increasingly on cellular therapeutic approaches to the treatment of patients with cancer. The Serody laboratory developed novel mouse models to evaluate the function of checkpoint inhibitor therapy such as anti-PD-1 mAb treatment and worked with the informatics group at the Lineberger Comprehensive Cancer Center, led by Joel Parker PhD, to evaluate genomic approaches as biomarkers for response to checkpoint inhibitor therapy. In collaboration with two new recruits brought to UNC-Chapel Hill from The Baylor College of Cell and Gene Therapy, Barbara Savoldo MD PhD and Gianpietro Dotti MD, Dr. Serody has led clinical efforts to bring CAR T cell and other cellular therapies to the University of North Carolina at Chapel Hill. This involved the development of a clinical grade Good Manufacturing Facility for the expansion of autologous T cells on Quadrangle Drive in Durham NC, and the opening of cellular therapy treatment protocols for patients with relapsed/refractory Hodgkin lymphoma and anaplastic large cell lymphoma at the University of North Carolina Cancer Hospital in 2016. This work led to the first patient in North Carolina being treated with CAR T cells that were manufactured in the state of North Carolina in July of 2016. Future clinical trials using CAR-T cell therapy for the treatment of patients with relapsed/refractory B cell leukemia and multiple myeloma will open in late 2016 or the middle of 2017.