Research

AIDS Clinical Trials Unit

Colorado Center for AIDS Research

Faculty Research Interests

Peter Anderson
UCD
Peter Anderson, Pharm D is interested in antiviral clinical pharmacology, mainly for HIV infection. Our research includes pharmacokinetic considerations for antiviral therapy including what biological factors alter pharmacokinetics and what implications altered pharmacokinetics has on drug efficacy and toxicity in patients. A specific area of interest is the clinical pharmacology of antiviral nucleoside analogs particularly that related to concentrations of the active intracellular triphosphate moiety and clinical implications of such concentrations. Dr. Anderson's expertise is in measuring, interpreting, and analyzing antiretroviral drug concentrations in patients.
Mary Bessesen, MD
VA Medical Center
Mary Bessesen, MD, Associate Professor. Dr. Bessesen serves as Section Head of the Division at the Denver Department of Veterans Affairs Medical Center. She directs the care of over 300 HIV- 1 infected individuals at the VAMC and has completed projects investigating prophylaxis of Pneumocystis carinii pneumonia, describing the role of Mycobacterium genavense as a pathogen in advanced HIV disease and demonstrating the cost-effectiveness of antiretroviral therapy. She also supervises the Infection Control program at the Veterans Eastern Colorado Health Care System and is pursuing research interests in Staphylococcus aureus carriage, invasive disease and control measures, and Clostridium difficile disease.
William Burman, MD
Denver Health and Hospital Authority
Dr. William Burman Is an Associate Professor of Medicine and the Medical Director of the Infectious Diseases Clinic of Denver Public Health. He received his Infectious Diseases training at the University of Colorado. His research has focused on the design and Implementation of randomized clinical trials to Improve treatment of HIV disease and tuberculosis. Dr. Burman has been the chair of the science planning committee of the Tuberculosis Trials Group (TBTC), an International multicenter clinical trials group, since It Inception In 1997 and chaired two studies. He helped found and remains an active member of the pharmacokinetics working group of the TBTC's pharmacokinetic working group. The goal of the TBTC Is to develop much shorter and better tolerated regimens for the treatment of active and latent tuberculosis. Dr. Burman Is also an active Investigator In the Community Programs for Clinical Research on AIDS, being the chair of two substudies of the large International Strategies of Management of Antiretroviral Therapy (SMART) trial. Finally, he remains active in local studies of adherence to antiretroviral therapy.
John C. Cambier, Ph.D.
National Jewish Medical and Research Center
John C. Cambier, Ph.D. is interested in transmembrane signal transduction mechanisms underlying the regulation of lymphocyte and mast cell responses to antigen and other environmental cues. Our work is currently focused on five specific problems: 1) the basis of antigen unresponsiveness of anergic B cells, 2) the mechanism of signal regulation by feedback mechanisms and inhibitory receptors such as Fc?RIIB, 3) the molecular circuitry that is activated by HIV gp120 and leads to T cell death by apoptosis, 4) the cause of cessation of B lymphopoiesis in aging, and 5) homeostatic regulation of the B cell compartment. These studies which are pertinent to autoimmunity, immunodeficiency and immunosenescence. They involve primarily biochemical and biologic analyses used in conjunction with reverse genetics in mouse models.
Thomas Campbell, MD
UCD
Thomas Campbell, MD, Associate Professor. Dr. Thomas Campbell is an accomplished clinical investigator whose research has helped to improve treatment for HIV infection and to better understand the viral pathogenesis of Kaposi's sarcoma in sub- Saharan Africa. He was part of the ACTG committee that formulated the ACTG international research agenda in 2003. He is the Colorado ACTU Principal Investigator. He is Associate Program Director of the UCD Adult GCRC and Director of the Colorado CFAR Virology Core. His laboratory studies the epidemiology and molecular biology of Human Herpes Virus, the causative agent for Kaposis sarcoma.
Monica Carten, MD
UCD
Dr. Monica Carten is an Assistant Professor of Medicine and Medical Director of the Colorado AIDS Education and Training Center. She received her infectious disease fellowship training at Rush-Presbyterian-St. Luke's Medical Center/Cook County Hospital in Chicago. She is the director of Women's Services within the University HIV Practice and is the coordinator for the health care worker bodily fluid exposure program in the Infectious Disease Clinic. Her research focus is the reproductive health of HIV-infected women with focus on contraception and pregnancy planning. Dr. Carten's research projects include investigation of safety and tolerability of newer contraceptive methods in HIV-infected women, the possible pharmacokinetic interactions of contraceptive hormones with antiretroviral agents, and changes in genital tract bacteriology in the setting of hormonal contraception.
David Cohn, MD
Denver Health and Hospital Authority
David Cohn is Associate Director of Denver Public Health and Professor of Medicine in the Division of Infectious Diseases at the University of Colorado Denver. He was previously Director of the Denver Metro Tuberculosis Clinic and the Denver Disease Control Service. Dr. Cohn has been active in research and treatment of HIV/AIDS since 1982, and founded the Denver Health Infectious Diseases/AIDS Clinic in 1984. He has been principal investigator of the Denver Community Program for Clinical Research on AIDS (CPCRA) since 1989, and is currently national chair of the Science Planning Committee and is a member of the CPCRA Management Team and Steering Committee. He has also been principal or co-principal investigator of AIDS/HIV surveillance in Colorado, and CDC-sponsored projects, including the Community-based Demonstration Project for HIV Prevention and Risk Reduction, Adult Spectrum of Disease, and HIV seroprevalence studies. Dr. Cohn is also a co-investigator in the CDC Tuberculosis Clinical Trials and Epidemiologic Studies Consortia.
Dr. Cohn's major clinical research interest has been in the treatment and prevention of opportunistic infections in HIV-infected patients, and in particular mycobacterial infections (Mycobacterium tuberculosis and M. avium complex) in all persons. More recently, he has focused his research efforts on long-term effectiveness and outcomes of highly active antiretroviral therapy. Dr. Cohn was a medical officer in the Global Tuberculosis Programme at the World Health Organization (WHO), participating in studies of HIV-related tuberculosis in Africa and global drug resistance surveillance. He continues to be a WHO consultant and serves on the TB/HIV Working Group. Other recent international work includes being a faculty member for the MTCT-Plus Program, as a trainer in Kenya, and he has previously worked on projects or consulted in Uganda, Zambia, Botswana, Ethiopia, and South Africa. He has served on the Tuberculosis Committee of the Infectious Diseases Society of America and on the CDC Advisory Council for the Elimination of Tuberculosis.
Elizabeth Connick, MD
UCD
Elizabeth Connick, MD, Associate Professor. Dr. Connick is an immunologist with a specific interest in the immunopathogenesis of HIV-1 infection. She has been involved in clinical trials, including the University of Colorado AIDS Clinical Trials Unit, as well as laboratory-based translational research studies of HIV-1 infection, for the past 12 years. She is well known for studies of immune reconstitution in HIV-infected individuals including immune reconstitution inflammatory syndromes and clinical trials of immune based therapies. She has a longstanding interest in both clinical and immunopathogenesis studies of acute and early HIV infection and is the Principal Investigator of the "Pathogenesis of Acute HIV Infection" program project grant at UCDHSC. She has specific expertise in lymphoid tissue studies and is currently conducting lymphoid tissue studies to investigate the underlying basis of three distinct phenomena: 1) sex differences in HIV-1 viral loads; 2) HIV-1 replication within lymphoid tissues of individuals with sustained virologic suppression in plasma; and 3) evasion by HIV-1 of immune responses within lymphoid tissues. Dr. Connick is Associate Program Director of the University of Colorado GCRC Boulder satellite and Director of the Colorado CFAR Immunology Core, which provides flow cytometry and microscopy support to investigators at the University of Colorado.
Charles L. Daley, MD
National Jewish Medical and Research Center
Charles L. Daley, M.D. is the Head of the Division of Mycobacterial and Respiratory Infections at National Jewish Medical and Research Center where he is also a Professor of Medicine. Prior to coming to National Jewish, Dr. Daley was at the University of California, San Francisco where he was Chief of the Chest Clinic at San Francisco General Hospital and Medical Director of the CDC-funded F. J. Curry National Tuberculosis Training Center. While in California he was active in professional organizations serving as President of the California Thoracic Society and President of the California Tuberculosis Controllers Association. Dr. Daley is actively involved in clinical and epidemiologic investigations of tuberculosis and other mycobacterial infections. His specific research interests include the study of the molecular epidemiology of tuberculosis and investigations of new diagnostic and treatment approaches for mycobacterial diseases. Dr. Daley has served on committees focused on improving provider education and training in regard to the management of mycobacterial diseases. In addition, he has served on the writing committees for three national guidelines including, "Treatment of Tuberculosis," "Tuberculosis Control in the United States," and "Management of Nontuberculous Infections"; all developed by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America. In his new position at National Jewish, Dr. Daley plans to continue and improve upon the outstanding clinical care provided by the institution, expand the educational efforts of the Division, and build a research program focusing on mycobacterial and respiratory infections.
Charles Dinarello, MD
UCD
Dr. Charles Dinarello is a member of the National Academy of Sciences and is internationally renowned for his studies of the pathobiology of cytokines in a several disease states. Dr. Dinarello is credited with the characterization of IL-1 as well as the discovery of the IL 18 binding protein and rectly of the new cytokine, IL 32. He studies on the roles of cytokines in the immunobiology of infectious and inflammatory diseases have established the standard for the field. His studies on HIV 1 have been focused on the role of IL-18 in the regulation of HIV-1 expression.
Greg Everson, MD
UCD
Dr. Greg Everson received his M.D. degree from Cornell Medical College, NY, NY, in 1976. He is currently a Professor of Medicine and Director of Hepatology in the Division of Gastroenterology & Hepatology, Department of Internal Medicine, at the University of Colorado. Dr. Everson is a recipient of both NIH and industry-sponsored research grants and contracts to study liver disease, liver transplantation, and treat patients with hepatitis C. He is principal investigator of the NIH-sponsored HALT C trial and co-investigator of the NIH-sponsored A2ALL study of Living Donor Liver Transplantation at the University of Colorado Denver. He is an author and contributor to over 300 scientific and clinical publications related to hepatitis C, liver transplantation, and liver disease and has been an invited lecturer for local, regional, national and international meetings. He, in conjunction with his co-author, Hedy Weinberg, has authored 3 editions of Living with Hepatitis C: A Survivor's Guide, 1 edition of My Mom has Hepatitis C, 1 edition of Living with Hepatitis B: A Survivor's Guide, and 1 edition of Living with Hemochromatosis: Answers to Your Questions. Dr. Everson is a distinguished Fellow of both the American College of Physicians (fellow) and the American Gastroenterologic Association, and member of the American Association for the Study of Liver Disease, International Liver Transplant Society, and the American Society of Transplantation. He is past Associate Editor of Liver Transplantation and Journal of Lipid Research, and reviewer for numerous scientific and medical journals.
Courtney Fletcher, PharmD.
UCD
My research program is focused on the clinical pharmacology of antiretroviral agents, with a primary interest in quantifying the pharmacologic contribution, through pharmacokinetic, dynamic, and genomic studies, to variability in virologic response.
Sonia Flores, MD
UCD
Dr. Sonia Flores laboratory investigates the role of the cellular redox status on host defenses. The first project analyzes the effects of the HIV-1 transcriptional regulator Tat on the redox status of host cells and the consequences of such effects. The HIV-1 transcriptional regulator Tat is secreted from infected cells and taken up by uninfected cells. One of its downstream effects is to alter the cellular redox status by, among others, down-regulation of the human antioxidant enzyme Mn-superoxide dismutase (Mn-SOD). She is investigating the mechanisms of HIV-1 Tat-mediated inhibition of this important enzyme.
The second project in Dr. Flores' laboratory seeks to examine the mechanisms of one of the cardiopulmonary complications in AIDS: the presence of inflammatory infiltrates in the absence of any common pathogen. She is testing whether soluble Tat is partly responsible for this increased inflammation. She has found that normal human umbilical vein endothelial cells (HUVEC) exposed to Tat in vitro have increased E-selectin levels. The kinetics of this induction are being studied using a combination of inhibitors and activators of the endothelium. She is also studying Tat-mediated increases in endothelial cell permeability.
The third project in Dr. Flores' laboratory uses a model of chimeric SIV-HIV-nef (SHIV-nef) infection of Rhesus macaques to study pulmonary hypertension and vascular remodeling in the context of HIV infection. This laboratory has found that monkeys infected with SHIV-nef develop obliterative lesions in the pulmonary arteries that result in increased mean arterial pulmonary pressure and increased right ventricular hypertrophy. These lesions are not seen in SIV-infected monkeys, suggesting that specific HIV nef alleles are essential for the vascular remodeling. Monkeys are infected with SHIV-nef chimeric viruses and biomarkers associated with disease development are tracked. In vitro, cultured human endothelial cells are exposed to nef alleles as well as domain mutants to determine whether Nef affects cellular phenotypic and molecular characteristics.
Edward M. Gardner, MD
Denver Health and Hospital Authority
Dr. Edward M. Gardner, Assistant Professor of Medicine at the University of Colorado Denver, completed medical school at the University of Chicago - Pritzker School of Medicine, and his internal medicine training at the University of North Carolina Hospitals in Chapel Hill, NC. After four years in community health and correctional medicine he completed his infectious diseases training at the University of Colorado Denver. His main area of research interest is adherence to antiretroviral therapy for which he is funded by a National Institutes of Health Career Development Award (K01). His other areas of research interest include cost-effectiveness analysis, the impact of symptoms and adverse events on health outcomes in HIV infected patients, and the diagnosis and treatment of HIV infection. His clinical interests include treatment and complications of HIV infection and other infectious diseases with a special interest in the care of persons in correctional facilities.
Edward N. Janoff, MD
UCD
Dr. Edward N. Janoff, Professor of Medicine, Chief, Infectious Disease Division, Director, Colorado Center for AIDS Research (CFAR), received his Infectious Disease training at the University of Colorado and training in immunology at the National Institutes of Health. His work has focused on diseases of international importance, such as diarrheal disease, respiratory infections, and HIV-1/AIDS. Specifically, he has addressed the role of humoral immunity in defense against Giardia lamblia and Vibrio cholerae in the U.S., Thailand and Peru. Currently, Dr. Janoff and his team are characterizing mucosal responses to Streptococcus pneumoniae in the lung and to HIV-1 in the intestine, reproductive tract, and in breast milk. Each study is supported by a field site in Africa (Uganda, Burkina Faso, Botswana and South Africa) with collaborators from these African nations, England, France, and the United States. The goal of Dr. Janoff's laboratory is to provide a scientific foundation for mucosal vaccines to prevent pneumococcal infections and transmission of HIV-l /AIDS. Dr. Janoff laboratory focuses on the development of mucosal immunity to provide primary protection against infection, particularly HIV and Streptococcus pneumoniae. He integrates clinical and basic laboratory approaches to determine how pathogens interact with the host at the mucosal surface and how innate and humoral mechanisms, individually and in concert, serve to protect against infection. His primary model for mucosal defense against HIV involves post-natal transmission of the virus by breast milk. Based on epidemiologic, clinical and virologic and immunologic data from women in Burkina Faso, Botswana and Uganda, he is characterizing the role of pathogen-specific antibodies in blood and milk from transmitters and non-transmitters to neutralize autologous and heterologous HIV isolates, to prevent binding and uptake of these viruses by epithelial cells, as well as the mechanism of such inhibition. This work involves cellular, molecular, and biochemical approaches. For S. pneumoniae, he characterizes the systemic and mucosal response to natural infection and vaccine, the molecular basis for capsule-specific antibody responses (VH gene diversity and mutational pattern), and the functional activity of these human antibodies. The model involves the interaction of the bacteria with an without specific virulence factors (e.g., pneumolysin, IgA1 protease), complement, cytokines and chemokines, epithelial cells and phagocytes (neutrophils and alveolar macrophages). The goal is to develop effective vaccines against these pathogens to prevent infections where they begin, at the mucosa.
Steven Johnson, MD
UCD
Dr. Steven Johnson is a Professor of Medicine in the Division of Infectious Diseases at the University of Colorado Denver in Denver. After completing medical school at Northwestern University in 1984, Dr. Johnson completed the Internal Medicine Residency at Fitzsimons Army Medical Center in Aurora, Colorado, and the Infectious Diseases Fellowship at Walter Reed Army Medical Center in Washington, D.C. He was a staff physician in Infectious Diseases at Walter Reed from 1990-1994 and came to the University of Colorado in September 1994 to be Director of the Infectious Disease Group Practice and its HIV/AIDS Clinical Program.
Over the last 12 years, under his direction, the HIV/AIDS Clinical Program has grown from approximately 250 patients to over 1500 patients. This is a multi-disciplinary program which includes primary care, a pharmacy, a negative pressure area for inhalational treatments, a procedure area for acute care, and in-clinic consultants in Oncology, GYN, Endocrinology, Social Work, Mental Health, and Nutrition. An active quality improvement project has documented steadily improving outcomes in the program: the mortality rate of program patients has declined from 15% in 1994 to 1.5% in 2005, the hospitalization rate has declined from 3.3 inpatients days per patient per year in 1995 to 0.6 inpatient days in 2005. In addition to the Denver clinic, collaborative HIV clinics have been established in Grand Junction, Durango, and Pueblo. Dr. Johnson is one of two ID consultants for the Grand Junction clinic (monthly) and the sole consultant for the Durango (quarterly) and Pueblo (monthly) clinics. In addition to HIV care, the IDGP runs the International Travelers Health Service, the Outpatient Parenteral Antibiotic Therapy (OPAT) Program, and the Blood/Body Fluid Exposure Program for the University of Colorado Hospital.
Dr. Johnson was Medical Director of the Colorado AIDS Education and Training Center (AETC) from 1998 to 2004. He is currently Medical Director of the regional Mountain-Plains AIDS Education and Training Center. Through the AETCs, Dr. Johnson has conducted more than 100 educational events for HIV providers in 25 Colorado cities. He has given over 250 lectures over the last 12 years, including presentations at the Infectious Disease Society of America Meetings. He has lectured around the country and recently taught at an antiretroviral certification course for providers in India. He received the University of Colorado Infectious Disease Fellowship teaching award in 2000.
In addition to his clinical and teaching activities, Dr. Johnson is a sub-investigator in the Colorado AIDS Clinical Trial Unit. He has authored or co-authored 10 book chapters and has co-authored a number of educational products through the AIDS Education and Training Centers. Dr. Johnson has also been very active in the community chairing the Governor's AIDS council, and sitting on a number of state and city committees pertaining to HIV care and Ryan White funding. He is a Fellow in the IDSA, a Fellow in the American College of Physicians, a member of the HIV Medical Association, American Academy of HIV Medicine, and the International AIDS Society. He was named Outstanding Physician of the Year by the University of Colorado Hospital Medical Staff in 2005.
Dr. Judson
UCD
Dr. Judson received his MD from the University of Pennsylvania in 1968 and his house staff training from the University of Wisconsin Hospitals (internal medicine) and the University of Colorado (infectious diseases). He was an Epidemic Intelligence Service officer with the Centers for Disease Control from 1970-72. Dr. Judson is board certified in internal medicine, infectious diseases and preventive medicine. For over 30 years his research interests have concentrated on the epidemiology and control of sexually transmitted infections including hepatitis B and HIV infections. Dr. Judson has authored or co-authored more than 250 scientific publications. He recently has served as President of the International Society for STD Research (ISSTDR), a member of the Colorado State Board of Health, Chief of Infectious Diseases for the Denver Health Medical Center (1983-2002), and Director of the Denver Public Health Department (1986-2004). Currently, Dr. Judson is immediate past-president of the International Union Against Sexually Transmitted Infections (IUSTI), a Member of the Presidential Advisory Council on HIV/AIDS (PACHA), immediate past-chairman of the Board of the American Social Health Association (ASHA), and Professor of Medicine and Preventive Medicine at the University of Colorado.
Dr. Kedl
National Jewish Medical and Research Center
Dr. Kedl has recently demonstrated that immunization with antigen in the presence of agonists for both a Toll Like Receptor (TLR) and CD40 (combined TLR/CD40-agonist immunization) elicits a vigorous expansion of antigen specific CD8+ T cells that is exponentially greater than the response elicited by either agonist alone. This combined TLR/CD40-agonist immunization generates CD8+ T cell responses even in CD4 depleted or CD4 deficient hosts. Studies from other labs have indicated that while primary CD8+ T cell responses proceed normally in CD4 depleted or deficient hosts, memory CD8 responses are diminished 5-10 fold compared to wild type hosts. We now have data demonstrating that both primary and memory CD8+ T cell responses elicited by combined TLR/CD40-agonist immunization occur relatively independently of the presence of CD4+ T cells. Furthermore we have observed that, in contrast to treatment with either agonist alone, immunization with combined TLR/CD40 agonists leads to an increase in the expression of the TNF ligand family member CD70 on the surface of the major dendritic cell subsets within lymphoid tissue. This induced expression of CD70 on DCs is significant since blocking antibodies against CD70 are able to dramatically reduce the degree of CD8+ T cell expansion observed after combined TLR/CD40 agonist immunization. Surprisingly, Type 1 IFN also has a dramatic influence on the primary and memory CD8+ T cell response generated by some TLR agonist/anti-CD40 combinations. Collectively, our data demonstrates that the development of potent primary and memory CD8+ T cell immunity depends on the coordinated integration of the TLR, TNFR/TNFL, and type I IFN stimuli. The lab is currently focused on investigating the integration of these stimuli, the mechanisms by which these pathways elicit such potent cellular immunity, and methods for incorporating these data into novel therapeutic vaccine development.
John Koeppe, MD
UCD
Dr. John Koeppe is Assistant Professor of Medicine in the Division of Infectious Diseases at the University of Colorado Denver. He received his Infectious Diseases training at the University of Colorado Denver. In addition to caring for over 200 HIV+ patients as their primary care provider in the Infectious Disease Group Practice and VAMC he also provides outpatient consultation on various infectious disease questions, attends on the Infectious Disease Consult Service and in the Fellows Clinic on Tuesdays. He is director of the Outpatient Antibiotic Program and is involved in trials of the AIDS Clinical Trial Group.
His work focuses on reasons for ongoing morbidity and mortality in the era of Highly Active Antiretroviral Therapy, with a focus on mental illness and substance abuse.
Lisa Kosminski MD
UCD
Dr. Lisa Kosmiski, Associate Professor of Medicine received her endocrinology training at the University of Colorado Denver in the Division of Endocrinology, Metabolism and Diabetes. Currently, her research interest is HIV lipodystrophy. Specifically, she is interested in the observation that patients with HIV lipodystrophy have increased basal metabolic rates. Advances in this area could lead to a better understanding of the role of subcutaneous fat and the nutritional requirements of patients living with HIV lipodystrophy. Dr. Kosmiski also does some basic science research looking at the effects of medications used to treat HIV infection on the health of fat cells.
Marilyn E. Levi, MD
UCD
Dr. Marilyn E. Levi is Associate Professor of Medicine in the division of infectious diseases at the University of Colorado Denver. She received her Infectious Diseases training at the University of Texas Southwestern Medical Center. Her work focuses on transplant infectious diseases, with a specific interest in viral complications of transplantation including the treatment of multiresistant cytomegalovirus with novel agents, Epstein Barr virus and posttransplant lymphoproliferative disorder. She also attends in the Infectious Diseases Group Practice Clinic at the University of Colorado Hospital and is involved in trials of the AIDS Clinical Trial Group.
Myron J. Levin, MD
UCD
Myron J. Levin graduated from Harvard Medical School in 1960. He completed a residency in Internal Medicine at the Bronx Municipal hospital Center (Einstein Medical School), and spent the next three years at the National Institutes of Health. The last two years at NIH were devoted to research in molecular virology. Dr. Levin returned to Harvard in 1969 to complete a fellowship in Infectious Diseases with the combined adult-pediatric training program at the Children's Hospital and the Beth Israel Hospital.
In 1976 he became the first Chief of Infectious Diseases at the Sidney Farber Cancer Center (now the Dana-Farber Cancer Institute). From 1982 to 2000 he was Chief of Pediatric Infectious Diseases at the University of Colorado School of Medicine and the Children's Hospital of Denver, and Director of the Clinical Virology Laboratory at the University of Colorado Hospital. Dr. Levin's clinical interests are in antiviral therapy, the immune response to herpesvirus infections, and vaccinology (especially the immunology of vaccines). His laboratory studies focus on latency of herpesviruses in human neurons. Dr. Levin has authored 285 original articles and edited 6 books. He recently co-authored a report that led to the licensure of a live vaccine to prevent herpes zoster in older individuals. In 2005, Dr. Levin completed five years as a member of the Advisory Committee on Immunization Practices (CDC), serving as its Chair for the last two years. Dr. Levin directs a clinic at his medical school for research on experimental vaccines and antiviral drugs.
Nancy Madinger MD
UCD
Nancy Madinger MD, Associate Professor. Dr. Madinger directs the Postgraduate Training Program of the Division of Infectious Diseases and also serves as the Director of the Clinical Microbiology Laboratory of the University of Colorado Hospital. Her research area is in diagnostic clinical microbiology, including antimicrobial susceptibility testing, molecular microbiology and its clinical applications, and molecular epidemiology of noscomial infections.
Dr. MaWhinney
UCD
Dr. MaWhinney is an Associate Professor of Biostatistics with a primary appointment in the Department of Preventive Medicine and Biometrics. Her graduate training was in Biostatistics at Harvard School of Public Health (HSPH). Before coming to UCD in 1994, she completed post-docs at the Institut National de la Santé et de la Recherche Médicale (Paris France) and at HSPH working, in part, for the AIDS Clinical Trial Group (ACTG). Her primary research interests are developing statistical methods for immunological, virological and infectious disease data with a current focus on longitudinal analyses utilizing varying-coefficient models. Dr. MaWhinney has served as the primary mentor for 6 MS and 4 PhD students and has served as a committee member for over 21 students at UCHSC. She has co-authored papers with 6 of 8 of her past students. Dr. MaWhinney is actively involved in interdisciplinary research. She has co-authored 28 infectious disease / immunology papers in epidemiological methods (HIV/AIDS, Bovine Spongiform Encephalopathy (Mad Cow Disease), Creutzfeld Jakob Disease / Chronic Wasting Disease), statistical methods for the analysis of immunological assays and HIV/AIDS clinical trials. She is also an associate editor for the Journal of Clinical Virology. In 2005, Dr. MaWhinney was awarded a grant from the UCD Center for AIDS research to fund statistical methods research in collaboration with local HIV/AIDS investigators. Recently, Dr. MaWhinney received an Interdisciplinary Grant in the Mathematical Sciences NSF grant which will enable her to spend one year (8/1/07-7/31/08) studying immunology and virology, primarily at UCHSC.
Dr. McFarland
Children's Hospital
Dr. McFarland is the Director of the Children's Hospital HIV Program which serves HIV-affected infants, children, youth, pregnant women, and families. She is a co-investigator for the Pediatric AIDS Clinical Trials Group (NICHD) and Ryan White (HRSA) Title IV grants. She is co-PI of an IMPAACT Immunology Specialty Laboratory (NICHD) and serves as vice-chair of the IMPAACT Vaccine-Immunology Research Agenda Committee. Her primary areas of research interest are HIV vaccines for prophylaxis and immune-based therapy, the role of HIV-specific cell-mediated immunity in HIV pathogenesis and response to therapy. She serves as clinical consultant 6-8 weeks per year (240 hr/year; includes daily microbiology rounds, inpatient rounds with fellows, three times weekly didactic talks). She attends in the outpatient ID clinic every other month (5hr/clinic, 30hr/year). She also attends in the HIV clinic once per month (10 hr/clinic including a permanent panel of patients), and attends the weekly case management rounds for HIV patients. She assists the Fellows in coordinating a didactic lecture series regarding pediatric HIV topics, and in identifying key publications and internet site resources to enhance their knowledge of HIV. She maintains a mentoring system for HIV training in which each fellow is matched with a particular set of HIV patients, so that they can participate in continuity of care for HIV-infected patients and can receive more personalized instruction in HIV care issues. Each year she updates the HIV program orientation packet that is provided to the Fellows in July. The packet includes key information to assist the Fellows in covering off-hours calls from HIV patients. She participates in research conferences (monthly); journal club (every two months); participates in the Didactic Lectures for HIV Infectious Diseases (two per year), and participates in the weekly case management rounds (3 hr/week). In addition she attends an HIV research conference sponsored by the CFAR (weekly) and journal club (monthly). A subset of Fellows participating in HIV-related research attend these conferences, She lectures at the PID/ID fellows lecture series (Monday 7:30am; one per year).
Terrance Potter, PhD
National Jewish Medical and Research Center
The primary focus of Terrance Potter, PhD lab is the role of the CD8 coreceptor during T cell activation and thymic selection. We are examining the induction of apoptosis in a particular developmental stage of thymocytes. We have found that cross-linking of CD8 by antibodies or MHC class I molecules attached to a bead, on non-proliferating CD4+CD8+ thymocytes induces rapid apoptosis. We are currently characterizing the molecular events in this apoptotic pathway and the physiological role in T cell development. The trainees will participate in this research by performing additional in vitro experiments in which the levels of particular signaling intermediates is manipulated with siRNA in thymoma cell lines that we use to model the apoptotsis of thymocytes.
Randall Reves MD
Denver Health and Hospital Authority
Dr. Randall Reves directs a variety of research projects evaluating tuberculosis epidemiology.
Leland Shapiro, M.D.
V A Medical Center
Leland Shapiro, M.D. research interest is in alpha 1 antitrypsin (AAT), the most abundant serine protease inhibitor in the circulation, posesses inhibitoory effects in vitro or in vivo for several viruses (including HIV) and bacteria (including TB). AAT also appears to function as an endogenous inhibitor of inflammatory cytokines (such as TNF and IL-1), and inhibits in vitro and in vivo synthesis of nitric oxide and apoptosis. AAT inhibits anthrax toxin induced cytolytic activity by 100%, and In an in vivo model of murine islet cell allograft rejection, AAT blocked rejection when used as a single agent. We continue to expand our understanding of the biological activities of AAT. A primary focus is isolating the molecular target of AAT biological activity in an effort to understand the pleitropic functions of AAT and to design novel therapeutic drug candidates to exploit the therapeutic potential of AAT-like molecules.
We also investigate the antiretroviral activity of interleukin(IL) 18 in HIV production in vitro. In a companion clinical investigation of early HIV infection, we are examining the role of constitutive and stimulated whole blood IL-18 content in progression of HIV infection. IL 18 is a cytokine that likely initiates and sustains the Th1 like response, and is a potent inducer of interferon gamma production in vitro and in vivo.
Kenneth Tyler, MD
V A Medical Center
Dr. Kenneth Tyler uses reoviruses as an experimental model system to understand how discrete viral genes and the proteins they encode determine the capacity of viruses to produce disease in the host (pathogenesis) and injure cells. Reoviruses induce apoptosis in key viral target organs in vivo including the heart and CNS. Dr. Tyler has identified viral genes that play a key role in apoptosis, and is using both primary and continuous cell lines and mouse models of myocarditis and encephalitis to investigate cellular mechanisms and pathways of apoptosis. He has recently shown that reoviruses activate transcription factors including NFkB and c-Jun, and that this activation plays a key role in apoptosis. He is currently using genomic and proteomic approaches to identify cellular genes and proteins induced following viral infection that play a critical role in apoptosis and cell cycle dysregulation. In epithelial and cancer cells lines, reovirus-induced apoptosis involves the TNF superfamily of cell death receptors including DR4, DR5 and their apoptosis-inducing ligand TRAIL. He has recently mapped the pathways of caspase activation that occur following reovirus infection in both epithelial cells and primary neuronal cultures. In both types of cells, reovirus infection results in activation of the DR-associated initiator caspase, caspase 8. In epithelial cells, caspase 8 activation cleaves the Bcl-2 pro-apoptotic protein Bid, which in turn promotes mitochondrial release of pro-apoptotic factors including Smac/DIABLO and cytochrome c. Cytosolic cytochrome c promotes activation of caspase 9, and Smac/DIABLO promotes apoptosis by inhibiting the inactivation of cellular inhibitor of apoptosis (IAP) proteins. Mitochondrial pathways appear to be less important in neuronal cells, suggesting that the cellular pathways of apoptosis induced during viral infection differ in a cell-type specific manner. Studies are currently underway to analyze: (1) the cellular mechanisms involved in apoptosis induction including the role of MAP kinase signal transduction pathways, (2) gene and protein expression required for apoptosis, and (3) the effects of inhibiting apoptosis on pathogenesis in vivo, and (4) the role of specific viral proteins in virus-induced apoptosis and cell cycle dysregulation.
Linda van Dyk, MD
UCD
Dr. Linda van Dyk is characterizing host-pathogen interactions in gammaherpesvirus infection, with primary emphasis on latency and reactivation. The gammaherpesviruses are large DNA viruses that are typified by their ability to establish a lifelong latent infection in the lymphocytes of their hosts. Gammaherpesviruses control cell cycle, some by encoding cyclin genes in the viral genome. Dr. van Dyk has shown that transgenic expression of a viral cyclin encoded by a murine gammaherpesvirus is oncogenic in primary lymphocytes. She also determined that, in the context of in vivo infection, the viral cyclin is critical for reactivation from latency and for chronic disease. Dr. van Dyk is studying the mechanism of action of viral cyclins in reactivation from latency. Furthermore, she has recently identified p18Ink4c as the host factor which must be bypassed by the viral cyclin for reactivation to proceed. p18Ink4c is a tumor suppressor which plays an important role in latency and reactivation. Tumor suppressors act as sensors of cellular stress, therefore, tumor suppressors are likely activated by virus infection. The van Dyk laboratory is analyzing the interactions between gammaherpesvirus infection and tumor suppressors through genetic analysis and high-throughput drug screening of virus reactivation.
Virally encoded miRNAs were recently discovered by Dr. van Dyk and others. The role of these small non-coding RNAs in gammaherpesviruses is now being addressed through generation and analysis of a viral mutant which lacks all of the miRNAs.
Dr. van Dyk has also demonstrated that lymphocytes at different stages of differentiation are differentially susceptible to lytic infection. The murine gammaherpesvirus model system allows direct testing of the hypothesis that host signaling molecules are directly required for gammaherpesvirus latency and transformation. Dr. Van Dyk is studying host lymphocytes during virus infection to determine if host signaling facilitates the establishment of viral latency, and if so, to determine the nature of these pathways and molecules.
Andres Vazquez-Torres, MD
UCD
Dr. Andres Vazquez-Torres' laboratory is currently studying two aspects of the innate immune responses of macrophages to the intracellular enteric bacteria Salmonella typhimurium, which is a category B select agent for NIAID biodefense research.
Invasion of the gastrointestinal mucosa by Salmonella depends on a type III secretion system encoded by the Salmonella pathogenicity island 1 (SPI1). Paradoxically, SPI1-deficient Salmonella strains are capable of disseminating extraintestinally and causing lethal infection. Dr. Vazquez-Torres demonstrated that intestinal dendritic cells mediate the extraintestinal dissemination of SPI1-deficient Salmonella. These phagocytes not only provide an entry way for enteric pathogens, but they also induce systemic immune responses. He is currently investigating the anatomical location and molecular basis for the transmigration of Salmonella-containing phagocytes as well as the mechanisms by which intestinal dendritic cells trigger systemic immunity.
Phagocytes expressing NADPH oxidase and inducible nitric oxide synthase produce a wide array of reactive oxygen and nitrogen species that mediate innate resistance against many different pathogenic microorganisms. Many pathogens avoid the deleterious actions resulting from NADPH oxidase activity, for example by detoxifying the oxyradicals synthesized by this enzymatic complex or repairing the damage inflicted on the pathogens by these radicals. Dr. Vazquez-Torres has described a novel strategy used by endocytosed S. typhimurium to avoid contact with vesicles harboring functional NADPH oxidase, and he showed that it requires the contact dependent secretion system encoded by SPI2. His data suggest that effector proteins secreted by SPI2 prevent the contact of endocytosed Salmonella with NADPH oxidase by interrupting the TNF? signaling pathway of the host phagocyte. His data also strongly implicate priming of phagocytes via TNF? receptors as essential for vesicular trafficking of the oxidase into the Salmonella-containing phagosomes. He is currently identifying signals transduced by TNF? receptors that deliver NADPH oxidase-containing vesicles to the vicinity of phagosomes harboring Salmonella. In addition, he is characterizing the SPI2 effector proteins that antagonize this process.
Adrianna Weinberg MD
Immune restoration in HIV-infected patients has been the object of Adrianna Weinberg, MD studies for several years. As such, I established virologic correlates of immune reconstitution in children and adults, and identified immune correlates of protection against CMV infection in HIV-infected patients on HAART. I recently described an inhibitory mechanism of cellular immunity operative in HIV-infected patients, but not in healthy individuals. This is the current object of more in-depth studies at sub-cellular level. I developed several lines of investigation of CMV-specific immunity in transplant patients, including the following: impact of CMV infection on graft rejection;immune restoration in bone marrow transplant recipients and immune correlates of protection against CMV infections; use of dendritic cells for establishment of CMV-specific immunity in stem cell and cord blood transplant recipients.
Cara Wilson, MD
Cara Wilson, MD, Associate Professor. Dr. Wilson is an experienced cellular immunologist who investigates the role of dendritic cells and HIV-specific T cells in the control of HIV-1 replication and conducts clinical research on the development of novel HIV-1 therapeutic vaccines. Her research focuses on the immunopathogenesis of HIV-1 infection. Dr. Wilson is an expert in dendritic cell biology and the role of dendritic cells in HIV-1 pathogenesis. She also studies both helper and cytotoxic T-cell responses to HIV-1 and the induction of HIV-1 specific immune responses in vaccine development. Dr. Wilson has been a Co-Investigator in the Colorado ACTU since 1998. She currently serves as Vice Chair of the ACTG Translational Research and Drug Development Committee and is a member of the ACTG Immunology Support Laboratory Subcommittee.