Project 1: Paul Lambert | Timothy McCulloch
Project 2: Paul Harari | Gregory Hartig
Project 3S: Zachary Morris | Paul Harari
Project 4: Deric Wheeler | Randall Kimple
Project 1: Basic Science Leader
Paul Lambert, PhD
Co-leader, Project 1
Professor and Chair of Oncology
Director, McArdle Laboratory for Cancer Research
Dr. Lambert is the Howard M. Temin Professor and Chair of Oncology in the McArdle Laboratory at UW with active NCI funding (P01 and R01 that focuses on the role of human papillomaviruses (HPV) in human cancer). Dr. Lambert is internationally recognized for his many contributions to understanding the role of HPV oncogenes in cancer through the use of genetically engineered mice. Notable contributions include defining the individual and temporal roles of HPV oncogenes E5, E6 and E7 in cancer; identifying mechanisms of action by which these viral oncogenes cause cancer; and defining the role of estrogen and its receptor in cervical carcinogenesis. Of direct relevance to this HN SPORE, Dr. Lambert developed the first mouse model for HPV-induced HNC to help define mechanisms of action for HPV-16 E6 and E7 oncogenes as well as the importance of host genes/pathways. The Lambert Lab recently demonstrated that mice deficient in the Fanconi Anemia (FA) DNA damage repair pathway have increased susceptibility to HPV-induced HNCs, paralleling that of FA patients. The Lambert Lab also defined the importance of HPV-16 E7’s inactivation of the tumor suppressor pRb and the related pocket protein p107 in promoting HNC. The experience and knowledge gained by Dr. Lambert in developing genetically engineered mouse models for HPV-associated cancers, including HNC, will be key to his accomplishing the goals of Project 1. Dr. Lambert will also utilize his research expertise to serve Dr. Harari in fostering inter- and transdisciplinary collaboration and coordination of the translational activities of this SPORE.
Project 1: Clinical Science Leader
Timothy McCulloch, MD
Clinical Co-leader, Project 1
Co-leader of Career Enhancement Program
Professor and Chair, Department of Surgery
Dr. McCulloch’s clinical practice centers on the surgical management of patients with head and neck cancer (HNC). In addition, he has 25 years of research experience in the area of HNC, with 20 years of swallowing-related work, including a significant body of work on the neuromuscular control of swallow centering primarily on electromyography and manometry. This recent work is funded by an NIH R21/R33 grant, a five-year grant that will develop new diagnostic methods for dysphagia and will use innovative technology in hypothesis-driven clinical care planning. Additionally, Dr. McCulloch has conducted a large volume of clinically based HNC care research. He has been funded to evaluate new treatment for radiation-induced dysphagia (R01CA120950), the value of pioglitazone in the treatment of mucosal leukoplakia (N01-CN-35153 subcontract), the role of intra-arterial cisplatin in the treatment of advanced HNC and the effects of epoetin alfa on surgical management of HNC patients. Dr. McCulloch has been a partner in prospective and retrospective HNC research at three major cancer centers. He is a tenured faculty member of the University of Wisconsin Department of Surgery and has held leadership roles and maintained a busy HNC clinical practice throughout his career.
Project 2: Basic Science Leader
Paul Harari, MD
SPORE Director
Co-leader, Project 2
Director, Administrative Core
Professor and Chair, Department of Human Oncology
Dr. Harari is the Jack Fowler Professor and Chairman of the Department of Human Oncology and served for nine years as associate director of the UW Carbone Cancer Center (UWCCC). He serves as principal investigator for the Wisconsin Head and Neck SPORE, director of the Admin Core and co-leader for Project 2. Dr. Harari’s primary clinical and laboratory research efforts are focused on improving treatment outcome for patients with head and neck cancer (HNC). Areas of particular research emphasis include the interaction of molecular growth inhibitors combined with radiation and the use of conformal radiation treatment techniques to diminish normal tissue toxicity. Dr. Harari has served on the Radiation Therapy Oncology Group (RTOG) HNC Committee for 20 years and as PI or co-PI for a series of national and international HNC trials. His laboratory research program centers on HNC biology, and he has served as PI for NIH R29 and R01 laboratory research grants investigating HNC response and resistance mechanisms to radiation and molecular targeting agents, with particular focus on EGFR pathway inhibitors. In Project 2 of the HN SPORE, Dr. Harari will investigate a unique imaging and anti-cancer agent developed at the UW (CLR1404). Following detailed examination in animal models, a translational research strategy to explore the role of CLR1404 in combination with external beam radiation in locally recurrent HNC patients, will be carried out.
Dr. Harari is a seasoned administrative leader serving as chair of the Department of Human Oncology since 2007 and associate director of Translational Research for the UWCCC from 2007 until 2016. He served as director of the UW Radiation Oncology Residency Training Program from 1997 until 2007, chairman of the ASTRO Education Committee from 2004 until 2008 and chairman of the first ASTRO/ASCO/AHNS H&N Cancer Symposium in 2007. He currently serves on the ASTRO Board of Directors and is president of ASTRO for 2017. He is devoted to facilitating interactions between basic, translational and clinical cancer researchers and is deeply committed to the leadership of multidisciplinary research teams.
Faculty Profile | Research Page
Project 2: Clinical Science Leader
Gregory Hartig, MD
Clinical Co-leader of Project 2
Co-director, Developmental Research Program
Professor, Department of Surgery
Over the past 20 years, Dr. Hartig has functioned as the primary ablative and reconstructive head and neck cancer surgeon at the University of Wisconsin. He currently serves as vice chairman of the Division of Otolaryngology, Head and Neck Surgery and director of the Microvascular Surgery Fellowship. He and Dr. Paul Harari have worked to develop a strong and cohesive team committed to the multidisciplinary management of all head and neck cancer patients. Dr. Hartig’s recent research interests have focused on improving the viability and integrity of HN free flaps and utilizing the extensive UW HNC database to better define the role of selective neck dissection and limited parotid surgery. He is co-leader with Dr. Harari on the Wisconsin Head and Neck SPORE’s Project 2, “Therapeutic combination of CLR1404 with external beam radiation in recurrent head and neck cancer.” He is committed to continue providing fresh HN tumor specimens for expansion of the patient-derived xenograft repository and will actively screen and enroll patients on the phase I clinical trial for recurrent HNC patients to receive CLR1404. He is dedicated to HNC research and training programs and works closely with Drs. Thibeault and Rapraeger to recruit new study themes and investigators to the Developmental Research Program within the Wisconsin HN SPORE.
Project 3S: Basic Science Leader
Zachary Morris, MD, PhD
Co-Leader, Project 3S
Assistant Professor, Department of human Oncology
Biography: The efforts of Dr. Morris’s translational research laboratory focus on examining the mechanisms and pre-clinical testing of treatment approaches that combine radiation and molecular-targeted therapeutics to drive anti-tumor immune responses. His educational background is diverse and includes formal training in immunology, tumor cell biology, signal transduction, protein structural biology, biostatistics, clinical medicine, and early phase clinical trial development. He first conducted research as an undergraduate, working at Argonne National Laboratory over a four-year period. Subsequently, having earned a Rhodes Scholarship, he completed two Masters degrees at Oxford University and then an MD/PhD at Harvard Medical School where he trained under the mentorship of Prof. Andrea McClatchey. During his residency training in Radiation Oncology, he led three IRB-approved protocols for patient research including a prospective phase I/II clinical trial. At the same time, he conducted preclinical research as part of a collaboration that he spearheaded between the labs of Prof. Paul Sondel and Prof. Paul Harari. That research effort resulted in multiple first-author original research manuscripts and development of model systems that are now facilitating continued productivity in his own lab.
Through this training, he gained expertise in testing hypotheses using experimental approaches that are founded on robust in vivo studies in murine tumor models (syngeneic, genetically engineered, humanized, and immune suppressed) and augmented by ex vivo and in vitro approaches that include immuno-histopathology, cellular immune function assays, radio-sensitivity assays, flow cytometry, molecular biology, and protein biochemistry. This breadth and depth of research experience has enabled him to compete successfully for continuous research funding over the past five years including his selection as one of 11 recipients of the 2016 NIH Director’s Early Independence Award and more recently his selection as one of 12 members of the inaugural NIH Immuno-Oncology Translational Network (IOTN) and PI of a NIH Cancer Moonshot U01. As part of the latter award, he have taken on a role as co-chair of the NIH IOTN Radio-Immunology working group. While his primary focus is on the advancement of basic and translational research efforts in his laboratory, he continues to be active in clinical research, currently serving as PI for three early phase clinical trials at the UW Carbone Cancer Center. More recently, he has been recognized for his dedication to trainee mentorship and leadership, as reflected in his recent promotions to Program Director for the University of Wisconsin Bentson Translational Research Fellowship and Vice-Chair for the Department of Human Oncology.
Project 4: Basic Science Leader
Deric Wheeler, PhD
Co-leader of Project 4
Associate Professor, Department of Human Oncology
Dr. Wheeler is a tenured faculty researcher in the Department of Human Oncology at UW–Madison, where he is a member of the UW Carbone Cancer Center. His laboratory focuses on resistance to molecularly targeting agents and methods for overcoming this resistance. Further, his laboratory focuses on the identification of novel targets in head and neck, lung and breast cancer. His expertise includes cell biology, molecular biology, mouse models of cancer, signal transduction, antibody-based therapies of cancer and translational cancer therapeutics. In particular, his research focuses on combinatorial antibody based therapies to overcome resistance to cancer therapeutics. In recently published work, Dr. Wheeler’s laboratory has identified the receptor tyrosine kinase AXL as a highly promising molecular target in head and neck cancer, the focus of Project 4.
Project 4: Clinical Science Leader
Randall Kimple, MD, PhD
Clinical Co-leader of Project 4
Associate Professor, Department of Human Oncology
Dr. Kimple is an Associate professor in the Department of Human Oncology. He is a member of the UW Carbone Cancer Center and the UW Institute for Clinical and Translational Research. His research focuses on ways to improve treatment outcomes for patients with head and neck cancers. Specifically, his lab seeks to uncover molecular mechanisms leading to increased sensitivity to therapy in HPV-positive cancers and how to target therapeutic resistance in head and neck cancer.
Dr. Kimple’s lab utilizes cellular and mouse models that they developed, including patient-derived xenografts (PDX) and intrinsic resistance models to understand therapeutic response. He led the development and characterization of the head and neck PDX model system at the University of Wisconsin, has active collaborations with Dr. Deric Wheeler related to the role of AXL in cetuximab and radiation resistance and has ongoing research projects investigating the role of cancer-initiating cells in therapeutic resistance.
His clinical practice is focused on the treatment of patients with malignancies of the head and neck as a member of the UW Multidisciplinary Head and Neck Program. This program interacts regularly with head and neck surgeons, medical oncologists, radiologists, speech-swallow therapists and numerous other specialists depending upon the individual case. Dr. Kimple is active in the NRG Oncology Group, serves as principal investigator on several active clinical trials and institutional review board approved protocols and actively enrolls patients in both national and investigator initiated trials open at UW.