Internal Medicine; Infectious Disease
I am an attending physician on the Infectious Diseases service at Roswell Park Cancer Institute (RPCI). My clinical duties include inpatient and outpatient consultations at RPCI and on-call duties at Buffalo General Medical Center. In addition to providing clinical care, I teach medical students, residents and fellows in daily rounds and through formal didactic lectures. My primary research interest focuses on the epidemiology, pathogenesis, prevention and treatment of opportunistic infections in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation. In addition, I study the epidemiology, pathogenesis and transmission of colonization and infection by vancomycin resistant Enterococcus in patients with hematologic malignancies. My long-term goal is to define strategies to prevent transmission, determine virulence and decrease the mortality associated with these infections. Finally, I participate as a site principal investigator in several multicenter clinical trials.
I am a UB faculty member and one of the few advanced endoscopists in the Buffalo-Niagara region. I serve as the chief of endoscopy and director of advanced endoscopic services at Roswell Park Cancer Institute. My clinical interests are in the field of endoscopic oncology, and the medical conditions I treat include cancers and polyps of the gastrointestinal tract, Barrett’s esophagus, bile duct strictures and pancreatic cysts. I perform endoscopic procedures that diagnose, stage, treat and palliate malignant and pre-malignant conditions of the gastrointestinal tract such as endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, cholangioscopy, endoscopic mucosal resection, enteral stenting, ablation of Barrett’s esophagus and double-balloon enteroscopy. I am widely regarded throughout the Western New York physician community for my excellence in patient care, especially as it relates to advanced endoscopic procedures. I teach and train gastroenterology fellows and supervise fellows and residents in clinical research. My research interests include the optimal management of submucosal masses of the gastrointestinal tract and the effectiveness of enteral stents for malignant bowel obstruction. I am also interested in health services research as it relates to providing patients with advanced endoscopic procedures, and I am investigating the effect of an interventional endoscopist on surgical volumes. My team is also analyzing the effectiveness of combined endoscopic ultrasound with fine needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) vs. ERCP alone as an initial step in diagnosing patients with pancreatic cancer and symptoms related to the biliary tract. I have also contributed instructional videos on gastric hyperplastic polyps and pancreatic lymphoepithelial cysts to the Digital Atlas of Video Education (the DAVE Project) so that professionals in the field have access to information on optimally managing these disorders. One of my roles is to help develop the Buffalo Niagara Medical Campus (BNMC) as a destination for patients needing complex, high-end endoscopic procedures not currently offered in this region. Toward that goal, I seek to expand training opportunities for fellows in advanced endoscopic procedures at the BNMC.
I am a palliative care physician at Roswell Park Comprehensive Cancer Center (Roswell Park). I care for patients who have advanced cancer, helping to manage their pain and other symptoms and providing psychosocial support. I have expertise in managing refractory cancer pain, neuropathy, nausea, fatigue, dyspnea, mood disorders and the other symptoms patients with advanced cancer experience. I see patients in the Roswell Park outpatient palliative care clinic, and I conduct inpatient consults for patients admitted to Roswell Park. An important part of my care is helping patients identify their treatment options and preferences throughout the stages of their cancer treatment. I help my patients weigh the risks and benefits of further chemotherapy and invasive procedures, for example, to decide the best tailored approach to their care. In addition, I help patients plan their care in the event their health worsens. These conversations help ensure that medical teams understand and respect my patients’ choices. I am an active researcher. Immune checkpoint inhibitors have provided an exciting breakthrough for patients with advanced cancer, but they can come with serious toxicities. I focus my research on evaluating better ways to screen and diagnose these toxicities earlier and identifying risk factors which may predispose some patients to developing these immune-related toxicities. Many patients also experience serious neuropathic pain as a result of their treatments, which can be challenging to care for; I am working to identify new treatments for this condition. I am in the beginning stages of investigating advanced-care planning in patients who are often at risk of poor communication with their medical teams. These patients receive less information, and in turn ask fewer questions of their physicians, than other patients. As a result, they may not receive the care that is truly consistent with their wishes. My goal is to educate medical teams to recognize high-risk patients and ensure that these patients receive the information they need. I teach medical students and residents. I lead small group discussions for third- and fourth-year students on advanced-care planning strategies. I also provide lectures and board review to the internal medicine residents.
I am a physician board-certified in internal medicine and medical oncology. I care exclusively for adult patients diagnosed with acute leukemias, myelodysplastic syndromes, chronic myeloid leukemia, chronic myeloproliferative disorders and other bone marrow disorders. I care for people diagnosed with these illnesses who are hospitalized at Roswell Park Cancer Institute or who come to the leukemia service at Roswell Park for outpatient care. I have an active translational research program. My research interest is focused on understanding more about the role of the immune microenvironment in facilitating persistent disease in acute myeloid leukemia. My goal is also to develop novel immunotherapeutic strategies for this disease. I invite interested students to my lab to collaborate with me in conducting research. I am responsible for supervising, teaching and mentoring medical students, internal medicine residents and hematology/oncology fellows at Roswell Park. I lecture to the hematology/oncology fellows as part of their curriculum and to residents rotating on the leukemia service. My focus during these lectures is mainly myeloid malignancies. I also teach and train at the bedside with the fellows, residents and students who are on service with me, and I teach and train in clinic settings as well. Given my expertise, I am able to provide trainees with comprehensive knowledge about how to render the best possible care for individuals diagnosed with bone marrow disorders, a medically complex patient population.
Infectious Disease; Oncology
I care for hospitalized patients and outpatients at Roswell Park Cancer Institute (RPCI), where I am head of Infectious Diseases. My area of clinical expertise relates to infections in patients with cancer and stem cell transplant recipients, and I have served on several national panels that establish guidelines for preventing, diagnosing, and managing infections in these patients. I also have a specific interest in patients with primary phagocytic disorders (e.g., chronic granulomatous disease). RPCI is the site of my clinical teaching. I also teach medical students in lecture settings and in small group sessions in their first and second years, including courses in lung pathophysiology and microbiology-immunology. We intermittently have students in our lab and participate in a grant designed to encourage medical students to become physician-scientists. I mentor residents in their clinical training and in research. I also teach fellows in all aspects of their training and mentor those who perform their research projects in my lab. I have an active, nationally funded translational research program. The major focus of our lab is studying NADPH oxidase as a critical regulator of inflammation and host defense. NADPH oxidase is an emergency host defense pathway that is rapidly activated in response to certain microbial products, and converts molecular oxygen to superoxide anion and downstream reactive oxidant intermediates (ROIs). Chronic granulomatous disease is an inherited disorder of the NADPH oxidase characterized by severe bacterial and fungal infections (e.g., invasive aspergillosis) and by excessive inflammation. In addition to its critical host defense role, our lab, in collaboration with colleagues, found that NADPH oxidase also functions to restrain inflammation by modulating redox-sensitive innate immune pathways. NADPH oxidase also affects T-cell responses, including the balance between Tn17 and regulatory T-cells. We have an NIH grant to further elucidate mechanisms by which NADPH oxidase regulates inflammation. We believe that our work has broad relevance to human diseases associated with inflammation, such as inflammation-induced injury and tumor immunology. Indeed, several of the pathways that NADPH oxidase regulates are important in tumorigenesis and the tumor microenvironment (e.g., NF-kB, Nrf2, IL-17, Tregs), and are potential therapeutic targets. In collaboration with colleagues, we are examining how NADPH oxidase influences tumor immunity.
Endocrinology, Diabetes and Metabolism
I am a board-certified endocrinologist with a special interest in diabetes and thyroid- and cancer-associated endocrinological issues. My clinical expertise is in diabetes, thyroid nodules and the endocrine side effects of cancer drugs. I work in tandem with a team of nurses, certified diabetes educators (CDEs) and physicians to provide the best possible care to my endocrine patients. I see patients at UBMD Internal Medicine at the Conventus Center for Collaborative Medicine located on Main St. in Buffalo. I have a simple approach toward my patients: I want them to see me as a true friend for whom their health is a top priority. I get to know my patients by asking about their hobbies, travel plans and daily chores. I avoid medical terminologies so that we can communicate without confusion and develop as equal partners in their care. I believe that the relationships I develop with my patients, along with aggressive care, help prevent long-term complications and facilitate excellent diabetes-related outcomes--in many instances avoiding amputations or stopping diabetes from progressing to chronic kidney disease (CKD). My current research interests include checkpoint inhibitors (as a new cancer therapy), related endocrine dysfunction and the methods to recognize and manage these toxicities. I encourage residents and fellows to work with me on small research projects and present them at national meetings. I teach medical students and residents on topics related to endocrine issues in adult patients. I also lecture to residents and fellows on diabetes, thyroid disorders and endocrine-related cancers. I emphasize with all my trainees that patients benefit maximally if health care professionals work as a team: team work minimizes errors, and it also elicits new ideas.
Allergy and Immunology; Oncology
-Studies in this laboratory have established that trophoblast cells have developed two novel mechanisms of silencing MHC class II genes: an upstream negative-regulatory element controlled by two trophoblast specific DNA binding proteins, and repression of transcription of the class II transactivator (CIITA). Recently, some human tumor cells have been shown to have a trophoblast phenotype, in that CIITA and class II are not inducible with g-IFN or other cytokines. In collaboration with A. Latif Kazim and Carleton Stewart, RPCI, we have shown that tumor cell lines that are not responsive to g-IFN despite an intact g-IFN receptor and Jak-Stat signaling pathway, can be induced to express mRNA and cell surface class II with agents that acetylate histones and remodel chromatin structure. Unexpectedly, we found that class II induction by inhibitors of histone deacetylase occurred in the apparent absence of transcription of CIITA. Recent studies with mutant cell lines defective in established class II regulatory genes suggest the existence of a pathway independent of CIITA, the presumed master regulator of MHC class II. During these experiments, we also showed that the expression of two other molecules of immunological importance MHC class I and CD40 also were activated by histone deace-tylase inhibitors. Dr. William Magner has joined my laboratory recently and, together with Dr. Elizabeth Repasky, we extended these studies to different mouse tumor cell lines, and demonstrated by flow analysis the induction of MHC class I and II genes as well as the costimulator molecule CD40. We are exploring the spectrum of antigens expressed on tumor cells treated with histone deacetylase inhibitors including TGF-b receptors and tumor associated antigens. We are determining whether treated tumor cells administered in vivo show enhanced immunity and decreased tumorigenicity to subsequent challenge with wild type cells. In this regard, as first shown by Ostrand-Rosenberg, et al., mouse sarcoma I cells, when transfected with MHC class II, produce solid and long-lasting immunity to inoculation with wild type cells. Thus, these findings have significance in tumor escape mechanisms and the development of vaccines. We have explored the possibility that repressors of CIITA transcription exist in trophoblast and tumor cells, thus inhibiting class II expression and its induction by g-IFN. TGF-b1 and IL-10 are produced by all of the tumor cell lines we examined that were deficient in class II expression. Since these cytokines repress class II transcription by inhibiting CIITA transcription, the possibility of autocrine inhibition is suggested. The mechanisms of TGF-b repression may involve recruitment of deacetylase enzymes to the class II promoter site by CREB-CBP-CIITA complexes. This possibility will be explored using chromatin immunoprecipitation techniques. Studies have been initiated on the role of transcriptional cofactors with histone acetyltransferase activity, as well as the role of ATP-dependent multiprotein chromatin remodeling complexes in regulating MHC gene expression. Our work also has demonstrated that TGF-b can bind to receptors on dendritic cells and inhibit antigen presentation. Moreover, serum TGF-b1 levels are elevated in AIDS and DC cells derived from the blood of HIV patients who have high levels of cell surface TGF-b1. Treatment with anti-TGF-b, or anti-type III TGF-b receptor antibodies, or the addition of GM-CSF reverses the defect in antigen presentation in AIDS-PBL in vitro. Prelimin-ary clinical studies in patients with advanced AIDS, in collaboration with the Department of Medicine, have shown that GM-CSF reverses the antigen presentation defect and significantly raises CD4 cell numbers in many, but not all, AIDS patients. To test the hypothesis frequently quoted in the literature that aberrant expression of class II antigens on fetal trophoblast cells is responsible for most spontaneous abortions, transgenic animals are being prepared that will express class II on placental trophoblast cells at a specific time during gestation. We have cloned 300 bp of the proximal promoter of a trophoblast specific gene, 4311, and placed this in an expression plasmid upstream of the full-length CIITA gene. This construct was shown to be active when transfected into freshly isolated mouse spongiotrophoblast cells. Thus, mice bearing this transgene should begin to transcribe CIITA at day 6 of gestation when the 4311 gene is first expressed. If the hypothesis is correct, then MHC class II should be expressed by day 7-8, and abortion would occur. A dominant negative of CIITA has been produced by deletion of part of the activation domain of CIITA, and this could potentially be expressed in trophoblast cells of strains with high abortion rates. If as postulated by others, fetal loss in these abortogenic strains is due to aberrant expression of CIITA and subsequently class II, the dominant negative should inhibit abortions in these mice.