Faculty

Randall Basaraba | John Belisle | Patrick Brennan | Delphi Chatterjee | Dean Crick | Mary Ann DeGroote |Karen M. Dobos | Torsten Eckstein | Mercedes Gonzalez Juarrero | Marcela Henao-Tamayo | Julia Inamine | Angelo Izzo | Mary Jackson |Nicole Kruh-Garcia | Anne Lenaerts | Michael Lyons | Jennifer McLean | Mike McNeil | Francisco Olea-Popelka | Diane Ordway | Ian Orme | Brendan Podell | Richard Slayden | John S. Spencer

Dr. Randall Basaraba
Randall.Basaraba@ColoState.EDU | website

Dr. Basaraba received his DVM degree from the College of Veterinary Medicine at Washington State University (WSU) in 1985. After a short time in a private, mixed veterinary practice in Chugiak Alaska, Dr. Basaraba returned to WSU and completed his PhD graduate degree in 1991 in the Department of Veterinary Microbiology and Pathology. Dr. Basaraba was certified by the American College of Veterinary Pathologists (ACVP) in 1992 while holding a faculty position in the College of Veterinary Medicine at Kansas State University from 1991 till 1999. In 1999 he accepted his current position as associate professor in the Mycobacterial Research Laboratory and the Department of Microbiology, Immunology and Pathology in the College of Veterinary Medicine and Biomedical Sciences at Colorado State University.

Dr. Basaraba has an interest in animal models of human tuberculosis (TB) with a special interest in human and animal TB pathology, lesion pathogenesis and in vivohost-pathogen interactions. Dr. Basaraba’s recent interests include modeling Mycobacteria tuberculosis(Mtb) infection in animals with concurrent, noncommunicable diseases know to be TB risk factors in humans. In particular, Dr. Basaraba’s laboratory has developed the first model of Mtb infection in guinea pigs with diet-induced type 2 diabetes. This model is being used to better understand the basic pathogenesis of TB / type 2 diabetes comorbidity and to test both TB and diabetes drugs to better control Mtb infection in diabetics. His laboratory is also interested in using the diabetic guinea pig model to test candidate TB vaccines intended for use in humans. Dr. Basaraba’s laboratory is also studying the molecular mechanisms of in vivo drug-tolerance expressed by Mtb especially when associated with macromolecules derived from necrotic host cells. Dr. Basaraba’s laboratory has developed a novel in vitro model of Mtb drug tolerance that is currently being used to test new TB treatment strategies. These include new antimicrobial drugs and drug combinations as well as novel adjunct therapy that can be used to potentiate existing TB drugs.

Dr. John Belisle
john.belisle@ColoState.EDU | website

Dr. Belisle is Professor of Bacteriology in the Department of Microbiology, Immunology and Pathology. He received his PhD from Colorado State University in 1992, performed a Post Doctoral Fellowship at University of Texas Southwestern Medical Center and became a member of the faculty at Colorado State University in 1995. Dr. Belisle was named a Monfort Professor by Colorado State University in 2003, and was named an Honorary Scientist of the National Veterinary Research & Quarantine Service of The Republic of Korea in 2006. He has served on multiple national or international advisory boards or expert panels addressing various aspects of tuberculosis research, as well as multiple NIH Study Sections. Dr. Belisle served as the Director of the MRL from 2002 to 2009 and has served as the Director of the Rocky Mountain Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research since 2007.

The laboratory of Dr. Belisle has focused on the characterization of the physiology of bacterial pathogens (in particular Mycobacterium tuberculosis, Mycobacterium leprae and Francisella tularensis) and how products of these bacteria interact with the hosts. These research activities have included the purification and characterization of bacterial proteins, lipids, and glycolconjugates; discovery of diagnostic and vaccine antigens; and the definition of specific molecular interactions involving the innate immune response. In performing and directing this work Dr. Belisle’s laboratory has utilized and developed numerous analytical techniques and methodologies that include mass spectrometry, liquid- and gas-chromatography, and electrophoresis. Current funded research foci in Dr. Belisle’s include: 1) the study of posttranslational modifications of mycobacterial proteins and the interaction of these and other macromolecules with the immune response against M. tuberculosis and M. leprae; 2) investigation of the involvement of protein posttranslational modifications in regulation of lipid synthesis in M. tuberculosis; and 3) applying metabolomic and lipidomics approaches to develop biosignature and biomarkers for assessing treatment response in tuberculosis patients as well as novel diagnostics.

Dr. Patrick Brennan
Patrick.Brennan@ColoState.EDU | website

Dr. Patrick Brennan was born in Boyle, County Roscommon, Ireland, in 1938 and completed his secondary education at Blackrock College, Dublin. He graduated from University College Cork (National University of Ireland) with the degrees of B.Sc. Honours (1961) and M.Sc. (1962) before arriving at Trinity College Dublin to undertake research, leading to the degree of Ph.D. (1965), on the mode of action of the anti-tuberculosis drug, Isoniazid. His research work was supervised by Professor Frank G. A. Winder and the work was carried out in the Medical Research Council Laboratories (long since demolished and replaced by the O’Reilly Institute) which already had a high reputation for research in the areas of tuberculosis, leprosy and cancer. This was followed by a two year postdoctoral fellowship at the University of California (Berkeley) studying the structures and biosynthesis of the phosphatidylinositol mannosides of Mycobacterium tuberculosis (the infectious organism causing tuberculosis). He returned to TCD as a Research Lecturer in November 1967 and the following year was married to Dr. Carol Blair who was a postdoctoral fellow in Biochemistry and subsequently Lecturer in Microbiology (1970-’75).

Patrick served as a College Lecturer at UCD (1971-’76) but then left Ireland for the USA to join his wife Carol who had been appointed an Assistant Professor at Colorado State University. He held senior posts in the National Jewish Centre for Immunology and Respiratory Medicine and the University of Colorado School of Medicine in Denver before being appointed Associate Professor, Professor and ultimately University Distinguished Professor at Colorado State University (Fort Collins). He founded a major research centre to study Mycobacteria and has published more than 300 peer reviewed papers on Tuberculosis and Leprosy. The outstanding quality of his research, together with his personal dedication to the elimination of leprosy and tuberculosis, is recognized throughout the world: He has served as Chairman of the World Health Organisation Program for Tropical Disease Research; research advisor to the Sasakawa Memorial Health Foundation who, through the Nippon Foundation, underwrites most of the Global Leprosy Elimination Campaign; and Chairman of the U.S.-Japan Cooperative Medical
Sciences Program.

Dr. Delphi Chatterjee
Delphi.Chatterjee@ColoState.EDU | website


Professor in Microbiology, Immunology and Pathology
Laboratory: C311 Microbiology Building | Office: C320 Microbiology Building
Academic Editor: PLoS ONE

 

Research Interests
Our research focuses on the glycomics and glycobiology of mycobacterial cell wall glycans such as lipopolysaccharides, glycolipids, and neutral glycans – playing important roles in the physiology and/or pathogenicity of Mycobacterium tuberculosis/leprae or in non tuberculous mycobacteria. Highlights from some of our work include definition of the structural attributes of lipoarabinomannan, a key lipoglycan ligand involved in host pathogen interaction; the identification of a number of glycosyltransferases (the Emb proteins), involved in the biosynthesis and polymerization of lipoarabinomannan; and the recognition of the pivotal role played by these glycosyltransferases in physiology and Ethambutol resistance.

Chatterjee Lab In addition, in the recent years, we have focused on understanding the unique state of Mycobacterium tuberculosis in granulomas and study the host response to granuloma formation in guinea pigs during the onset of infection. This is accomplished through highly collaborative studies within CSU (principally with the laboratories of Drs. Ordway, Orme, Crick, Basaraba, Dobos) and many others. Specifically, our laboratory utilizes high resolution magic angle spinning- nuclear magnetic resonance spectrometry (HRMAS-NMR), and solution NMR, animal models of tuberculosis, and infection with relevant clinical isolates.

A third exciting focus in our laboratory is on the development of point-of-care tuberculosis diagnosis tools that are based on innovative technologies such as selection of specific aptamers to secreted M. tuberculosisantigens (in collaboration with Drs. Dan Feldheim in CU) and Surface Enhanced Raman Spectroscopy (SERS) with Marc Porter in the NanoInstitute (Univ of Utah).

NMR Based Metabolics

Key Personnel in the Laboratory
Post-doctoral Fellows
Prithwiraj De
Pabitra Chatterji
Lorene Martinez
Senior Research Associate
Anita G. Amin
Research Scientist
Libin Shi
Undergraduates
Elyse Dowdy
Brianna Baca
Kelsey Holt

Dean Crick
Dean.Crick@ColoState.EDU | website

Dr. Dean C. Crick received his B.Sc. and M.Sc. degrees from the University of British Columbia, and his Ph.D. (Biochemistry) from the University of Western Ontario, Canada. He conducted his post-doctoral studies at the University of Kentucky under the supervision of Dr. C. J. Waechter. In 1998 he joined the faculty of the Department of Microbiology, Immunology and Pathology, at Colorado State University.

Dr. Crick has serves on CSU’s Radiation Safety Committee, the Infectious Disease Research Center Advisory Committee, Graduate Education Committee and The National Screening Laboratory for the Regional Centers of Excellence in Biodefense and Emerging Infectious Diseases Advisory Committee. In addition, he serves on the editorial boards of the Journal of Biological Chemistry and the Journal of Bacteriology.

The Crick laboratory currently has projects entitled: “HTS assays for the methylerythritol-4-phosphate pathway”, “Menaquinone biosynthesis: A drug target in gram-positive bacteria”, “Assembly of the mycobacterial cell wall” and “Sub-cellular composition mapping of a single bacterium by extreme ultraviolet laser ablation mass spectroscopy with nanometer resolution” funded by the National Institutes of Health. In addition, the Bill and Melinda Gates Foundation has funded the group to carry out a project entitled “Metabolomic responses of mice and non-human primates infected with M. tuberculosis”.

The research interests of the laboratory include biochemical studies on the structure and biogenesis of the cell wall and lipids of Mycobacterium tuberculosis, and to a lesser extent other bacteria and the laboratory also has a growing interest in metabolomic studies of infected animals and the bacilli living in the lungs of infected animals. Specific interests involve the metabolism of isoprenoids, one of the most structurally diverse and biologically important families of compounds known in nature, particularly the enzymes involved in isoprenoid metabolism involved in the cell wall and lipid biosynthesis (such as prenyl phosphates and lipoquinones). An additional research focus is on the enzymes that transport (flip) activated prenyl phosphate-linked saccharides across bacterial membranes in pathogenic organisms. Information gained in these studies is applied to identification of potential drug targets and the development of new anti-tuberculosis agents when feasible.

Current members of the laboratory include graduate students Fabio Fonte and Hana Gatlawi; postdocs Nurul Islam, Venugopal Pujari, Kelly Resmer, Ashutosh Upadhyay, Hongliang Yang and Lanhao Yang. Undergraduate members of the laboratory include Kaylee Brown (HURS program) and Reese Hitchings.

Dr. Mary Ann DeGroote
maryann.DeGroote@ColoState.EDU | website

Dr. Mary Ann DeGroote is an Infectious Disease clinician who works at Colorado State University (CSU) in the Mycobacterial Research Laboratories. She is currently working on two areas related to the study of mycobacteria. One, with Dr. John Belisle, is the development of novel tuberculosis prognostic and diagnostic assays. The second area involves novel therapies for nontuberuclous (NTM) mycobacterial infections such as Mycobacterium abscessus andMycobacterium avium complex. She works closely with Dr. Scott Franzblau and colleagues on projects funded by the American Lung Association and NTMir and Cystic Fibrosis grants to find new drugs against Mycobacterium abscessus and other NTM. In addition to screening compound libraries for anti-NTM activity the group has begun to characterize the efficacy of the most promising agents in animal models. Testing of novel compounds is done under a grant awarded to Dr. Anne Lenaerts under an NIAID contract for preclinical services for the NTM.

In addition to this research, she has also strived to bring the basic scientists together with clinical and clinical trialist colleagues to strengthen research up and down the Colorado Front Range. Partners include Denver Health, National Jewish Health, UC Denver, industrial partners and CSU). The hope is to bring real discoveries closer to patients.

Dr. Karen M. Dobos
Karen.Dobos@ColoState.EDU | website

Dr. Karen M. Dobos received her PhD in 1996 at Colorado State University under the mentorship of Drs. Brennan and Belisle. She returned to CSU in 2002 to expand on her studies in descriptive, comparative studies of Mycobacterium tuberculosis and other NTMs in an effort to further vaccine and diagnostic assay development.

Dr. Torsten Eckstein
torsten.eckstein@colostate.edu | website

Dr. Torsten Eckstein received his masters at Humboldt-University Berlin in 1984 in Germany and his Ph.D. at the National Academy of Sciences in 1987 in Germany. He further went onto receive his MD in Humboldt-University Berlin in 1987 in Germany and was Board Certified in Pediatrics in 1994.

Our laboratory focuses on research and education. For the latter, it is our mission to train undergraduate student in a new way that allows them to strongly compete for the best graduate programs in the US. It is our goal to recruit students as freshman or sophomore and guide them throughout the years until they graduate. Each student will be assigned to a specific research area. Usually, students start taking MIP 298 (Introductory Research – up to 4 credits). After one or two semesters, students will get paid for their research efforts. Most students will finish their research work with MIP 498 (Research – 3 credits) or MIP 495 (Independent Study – 3 credits). Some of our students are part of the CSU Honors Program and will finish their participation in our research with HONR 499 (Honors Thesis – 3 credits).

Our research focuses on the involvement of bacterial lipids in pathogenicity and virulence and how the bacterial lipidome could be used to identify new diagnostic tools and adjuvants. Since lipids are key molecules of every bacterium (pathogens and non-pathogens) we are not limited to a single pathogen or disease. Currently, we are working with four pathogen groups and their lipids: (1) Mycobacterium avium and its five subspecies (subsp. avium, subsp. hominissuis, subsp. paratuberculosis [type C and type S], subsp.silvaticum, subsp. lepraemurium), Mycobacterium bovis, Burkholderia spp. (B. pseudomallei, B. mallei, B. thailandensis), and Brucella spp. (B. abortus, B. suis, B. melitensis, B. ceti, B. pinnipedialis). In addition, we further developed the goat model for mycobacterial diseases with a strong emphasis on Johne’s disease and bovine tuberculosis.

Our current major project is a USDA sponsored research grant evaluating the immune response to immunogenic lipids of M. avium subsp. paratuberculosis in goats experimentally infected with this pathogen over at least three years. We obtained the goats two to five days after birth and infected half of them at the age of 7 weeks. Since then we follow their immune responses through standard tests and newly designed and developed diagnostic tests. We also evaluate the immune cell population changes through flow cytometry.

As a side project, we have in addition six goats, which we immunized with either M. bovis BCG (two goats) or B. pseudomallei Bp82 (two goats) and will immunize two more goats with B. abortus RB51.

Dr. Mercedes Gonzalez Juarrero
mercedes.gonzalez-juarrero@colostate.edu | website

Dr. Mercedes Gonzalez Juarrero interest is to study the basic nature of the cell mediated immune response to mycobacteria infections. During the last ten years we have undertaken studies to investigate the emergence of immunosuppression during pulmonary tuberculosis. We have focused mainly on how macrophages and dendritic cells in the M. tuberculosis infected lung become to express an immunosuppressive phenotype. We are able to modulate the lung immune environment by using intrapulmonary delivery of siRNA, recombinant cytokines and chemokines, antibodies and other immunomodulators. The main goal of our studies is to learn how and where we need to target the latently infected host to fully recover the antimicrobial activity of the infected cell and how we can use this information in the context of current chemotherapeutic and multidrug resistant TB infections. Our ultimate goal is to more rapidly eradicate drug tolerant and resistant bacilli using combined chemotherapeutic and immunotherapeutic approaches.

Dr. Henao-Tamayo
marcela.henao_tamayo@ColoState.EDU | website

Dr. Henao-Tamayo received her Medical Degree from the University of Antioquia, Colombia.  After finishing medical school, she joined a research group investigating genetic characteristics that could predispose to tuberculosis (TB). After that initial contact with basic research on a devastating global disease, she was determined to pursue a career in the field of TB. Marcela obtained a Master’s degree in Biomedical Sciences, with an emphasis on TB.  During that time in Colombia she met professors from Colorado State University and came to CSU as a visiting scientist.  She was later awarded a PhD by this institution, where she studied the cellular immune response to M. tuberculosis infection in mice and guinea pigs.

Currently she is an Assistant Professor at Colorado State University, Mycobacteria Research Laboratories, and the Co-Director of CSU-Flow Cytometry and Cells Sorting Core Facility.

Dr. Henao-Tamayo is interested in the immunopathogenesis of Tuberculosis. Using animal models, she evaluates the role of different types of T cells and Myeloid Derived cells in tuberculosis and BCG vaccination (Bacille Calmette Guerin, the only approved vaccine against TB). She has tested numerous vaccine candidates evaluating the immune response they elicit in association with protection against tuberculosis disease.

In the field of tuberculosis pathogenesis, her work has recently focused on evaluating murine models that develop necrotic granulomas in response to M. tuberculosis infection. These models are more akin to human pathology, thus they are a great tool to evaluate antibiotic and vaccine efficacy, as well as to identify pathogenesis mechanisms. Based on the immunopathogenesis of the disease she is currently evaluating immunotherapeutic approaches that combined with chemotherapy could improve the treatment of tuberculosis.

During the more than 15 years working in the filed she has used Flow Cytometry as valuable tool in her studies, and in 2015 Dr. Henao-Tamayo and Dr. Allan, received an Emerging Innovations Facilities award from the Vice President of Research at CSU to create a distributed, campus-wide flow cytometry core facility.

Dr. Julia Inamine
julia.inamine@colostate.edu | website

My laboratory is interested in the molecular genetic analysis of Mycobacterium species with regard to genes involved in drug resistance and virulence as well as the biosynthesis of cell wall components. Current projects focus on (1) genomic and proteomic analyses of M. avium subspecies avium and M. avium subspecies paratuberculosis, (2) comparison of the lipid and lipoglycan profiles of M. avium and M. paratuberculosis, and (3) the genetic analysis of Mycobacterium avium colony morphotypes and definition of the basis for drug resistance and virulence.

Dr. Angelo Izzo
angelo.izzo@colostate.edu | website

Dr. Izzo has over 20 years-experience in investigating the immune response to pulmonary Mycobacterium tuberculosis infection in animal models. Dr. Izzo obtained his PhD in Australia where he studied the immune response in humans to an inactivated whole cell vaccine against Q Fever. Upon moving to the United States in 1991, he began work as a Post- Doctoral Fellow under Dr. Robert North at the Trudeau Institute (Saranac Lake, NY) to investigate the immunopathogenesis of pulmonary tuberculosis in the mouse model. Dr. Izzo began a second Post-Doctral Fellowship in 1994 at the University of New Mexico (Albuquerque, NM), under Dr. Mary Lipsomb, working on animal models of Crypotococcus neoformans and M. tuberculosis to investigate pulmonary immunopathogenesis of these infectious diseases. During the past 10 years he has been a PI on the NIH Tuberculosis Vaccince Testing and Research Materials Contract (NIH HHSN266200400091c) where he has been investigating the immune response generated by novel vaccines against tuberculosis employing both the mouse and guinea pig models of tuberculosis.

Dr. Izzo’s research focus has been on understanding the immune response to infectious diseases and on vaccine induced immunity to infectious diseases, primarily Mycobacterium tuberculosis in several animal model systems including the mouse and guinea pig. He has identified key factors associated with the host/pathogen interaction and has extended these studies to the understanding of vaccine mediated immunity so as to identify key elements that are required for developing vaccines that provide long-lasting protective immunity. It may be possible to apply these key factors to other infectious pathogens.

In relation to vaccines, his laboratory continues to investigate the early signals that are required by a vaccine formulation to induce long-term protective immunity. To this end, the laboratory focuses on continuing to develop the animal model and maintaining its relevance to human disease. Additionally, work has been expanded to include investigations in human tuberculosis through a collaboration with National TB Reference Laboratory in Moldova.

Currently Dr. Izzo’s research is funded under the Animal models for testing vaccines against Mycobacterial Diseases RFP to continue testing vaccines in the mouse and guinea pig models of tuberculosis (HHSN272201000009I: Task A12: Advanced Small Animal Models for the Testing of Candidate Therapeutic and Preventive Intervention Against Mycobacteria).

Dr. Mary Jackson
mary.jackson@colostate.edu | website

Our research focuses on the elucidation of the mode of action of anti-mycobacterial inhibitors, the study of the mechanisms of resistance of slow- and fast-growing mycobacteria of clinical interest to antibiotics and disinfectants, and the biosynthetic pathways (enzymes and transporters) of major cell envelope components – (lipo)polysaccharides, (glyco)lipids, and fatty acids – playing important roles in the physiology and/or pathogenicity of Mycobacterium tuberculosis.

Dr. Nicole Kruh-Garcia
Nicole.Kruh@ColoState.EDU | website

Dr. Kruh-Garcia received her PhD in Molecular Genetics and Microbiology from Stony Brook University in New York. She joined the Mycobacteria Research laboratories at Colorado State University in 2007 as a postdoctoral researcher in Karen Dobos’ laboratory to characterize the proteome of Mycobacterium tuberculosis in the context of the guinea pig lung during infection. Dr. Kruh-Garcia’s work currently focuses three projects: 1. The use of unbiased and targeted mass spectrometry for the discovery and validation of bacterial protein biomarkers for the diagnosis of infection with Mycobacterium tuberculosis (in conjunction with the Dobos lab). We are also exploring the kinetics of mycobacterial proteins (within exosomes) in human biofluids and how this can be used to monitor drug resistance and reactivation of latent disease. 2. The development of quantitative targeted assays to measure cytokine and chemokine levels in guinea pig urine, as well as whole and depleted serum as a means to address the lack of available guinea pig immune reagents. 3. The study of cation transport in Mycobacterium tuberculosis and the downstream effects on pathogenesis.

Dr. Anne Lenaerts
anne.lenaerts@colostate.edu | website

Dr. Anne Lenaerts Ph.D., is Associate Professor of Microbiology, Immunology and Pathology at Colorado State University. She received her BSc [Biology], MS [Physiology, Biochemistry] and PhD [Molecular Biology] at the State University of Ghent, Belgium. After a postdoctoral position on TB research in South Africa and at SUNY in NY, she started in 2001 at CSU heading the Mycobacterial Drug Development program. The Lenaerts’ laboratory focuses on development and application of novel preclinical animal models to further both anti-tuberculosis drug discovery and study anti-mycobacterial resistance and persistence. She leads the NIH Drug testing Contract for Mycobacterial Infections (see link below) and is further independently funded by programs from the NIH, the Global Alliance for TB Drug Development, and the Bill and Melinda Gates Foundation. Her programs have assisted in the preclinical evaluation of PA-824, moxifloxacin, TMC207, the newer quinolones, clofazimine analogues, etc. to advance these TB drugs into clinical trials. Current research projects explore (1) development of new in vitro assays and animal models to optimize and accelerate TB drug evaluation, and (2) analysis of persistent mycobacterial populations with respect to location, pathology and drug responses through use of selective animal models.http://mrl.colostate.edu/acceleration/, http://www.niaid.nih.gov/labsandresources/resources/dmid/Pages/default.aspx

Dr. Michael Lyons
michael.lyons@colostate.edu | website

Dr. Michael Lyons work in the area between pre-clinical and clinical drug development for the treatment of tuberculosis. My focus is the development and application of mathematical and computational tools to better translate experimental studies to dose selection for clinical trials. This work involves both conventional pharmacokinetic/pharmacodynamic modeling and simulation as well as physiolgical modeling and the use of engineering-based and approaches to design of optimized combination drug regimens.

Dr. Jennifer McLean
jennifer.Mclean@colostate.edu | website

My research efforts are focused on gaining a better understanding of the immune correlates of protection against tuberculosis infection, particularly in terms of vaccine development. I work under Dr. Angelo Izzo on the TB Vaccine Testing and Research Materials contract, which is funded through the National Institutes of Health. The majority of our work is carried out in the Biosafety Level-3 facilities located in the Painter Center on the CSU campus and in the Biosafety Research Building on the foothills campus. COURSES TAUGHT: LIFE 205-Survey of Microbial Biology. LIFE 206-Microbial Biology Laboratory. MIP 192-Introductory Seminar. MIP 342-Immunology. TEACHING AWARDS: Provost’s N. Preston Davis Award for Instructional Innovation (2011) Innovative Instructional Methodology Award in Undergraduate Education (2011)

Dr. Mike McNeil
m.mcneil@colostate.edu | website

Research interests include TB drug development and the structure and biogenesis of the cell wall of TB. He has recently retired and shut down his laboratory but is continuing to work with other researchers in the MRL two days a week. Current interests include the structure of the TB cell wall in M. tuberculosis grown in experimental animals, the mode of action of inhibitors of cell wall biosynthesis, and efficacy of TB drug candidates in experimental animals.

Dr. Francisco Olea-Popelka
francisco.olea-popelka@colostate.edu | website

My international tuberculosis (TB) research program focuses on addressing challenges posed by mycobacterial infection shared by humans, livestock, and wildlife species in different environments, worldwide. An important component of my research philosophy is an integrated, multidisciplinary approach in which many factors, such as environmental, socio-economical, cultural, and political components are considered in conjunction with the disease causal agent and the host.

Below a summary of projects in which I am currently involved (Nov 2013):

• The study of factors relevant to the control of bovine and badger TB in Ireland, including wildlife ecology, BCG vaccination in badgers, meat inspection, and animal movement as it relates to the epidemiology of bovine TB.
• Assessment of bovine TB slaughter surveillance trace-back in the United States.
• The study of zoonotic TB among humans living at the livestock-wildlife-human interface in India, Kenya, South Africa, Uganda, and Zambia.
• Evaluation of non-tuberculous mycobacteria (NTM’s) infection in humans, livestock and wildlife.
• The assessment of socio-economic factors impacting the delivery of anti-tuberculosis drugs for TB patients in rural areas in Africa.
• Evaluation of screening/diagnostic methods for TB in lions and Cape buffalo in South Africa.
Mycobacterium bovis infection in cattle (bovine TB) in rural India, Kenya, Uganda and Zambia.
• Epidemiology of Mycobacterium tuberculosis in elephants in the United States.

As a result of my experience and work specifically related to TB, I was recently elected (November 1st 2013) as the Program Chair for the Zoonotic Tuberculosis sub-section at the International Union Against Tuberculosis and Lung Disease (The Union, http://www.theunion.org/), one of the world’s leading organizations providing health solutions for humans affected with TB and HIV. In this position, I will work towards increasing awareness of this zoonotic disease in high-risk rural areas of high-TB burden countries, globally.

With these applied research efforts, I seek to have a positive impact on health improving the prevention, diagnosis, and control of mycobacterial infection and TB in humans, livestock, and wildlife on a global scale.

Dr. Diane Ordway
d.ordway@colostate.edu | website | Rocky Mountain Immunology website
Videos hosted on Vimeo | Videos hosted on CSU’s YouTube channel

Dr. Diane Ordway finished her B.Sc in Microbiology at Colorado State University in 1992. Dr. Ordway received a full doctoral scholarship to attend the London School of Hygiene & Tropical Medicine receiving her Ph.D. in Infectious and Tropical diseases in 2000. Dr. Ordway is currently an Assistant Professor at Colorado State University, Mycobacteria Research Laboratory, Department of Microbiology, Immunology and Pathology and teaches immunology classes for students in undergraduate and graduate programs. Dr. Ordway is the head of the Flow Cytometry Unit and a certified operator of the LSR II Flow Cytometer and Mo Flow Dako cytometion and FACS Aria III cell sorting and analysis. Dr. Ordway has the expertise of being an immunologist with 18 years experience using and developing human and animal models of Mycobacterial infection. In addition, Dr. Ordway is one of the leading investigators evaluating whether the newly emerging MDR/XDR-TB strains of extremely high virulence are able to suppress the innate and/or acquired host response compared to other strains under a new innovative grant award. In addition, she also in apart of an NIH task order developing new nontuberculosis mycobacterial animal models. These animal models are used to test novel vaccines and drugs and provide us with information on the nature of induction of protective immunity http://www.rockymountainimmunology.com/.

Dr. Ian Orme
ian.orme@colostate.edu | website

A continuing objective of my laboratory is to develop relevant small animal models of tuberculosis, the world’s most devastating bacterial disease. Over the past decade we have made major contributions to understanding the basis of the pulmonary immune response to tuberculosis, using diverse technologies ranging from advanced flow cytometry to the use of mice in which specific genes have been selectively disrupted [gene-knockout mice]. In the guinea pig model, an animal that exhibits lung pathology very similar to that seen in humans infected with tuberculosis, we have systematically described the course of the infection using standard histology, immunohistochemistry, and magnetic resonance imaging. Our laboratory is the first to demonstrate the T cell mediated immune response in the lungs, using breakthrough flow cytometry. This information, collectively, is being applied to our vaccine development and drug screening programs. Amongst our recent achievements, we have described a new class of vaccines specifically targeting the Toll-2 receptor, and have described the apparent location of bacteria that persist in the lungs after prolonged drug treatment. These observations are providing the basis for new therapeutic approaches to treat this very serious global disease.

Dr. Brendan Podell
brendan.podell@colostate.edu | website

Dr. Podell’s laboratory emphasizes research in mechanisms of disease, pathogenesis, and pathology. These areas of study are applied in the development of animal models to better understand host-pathogen interaction, identification of factors influencing host susceptibility to infection, and for the identification of new host-directed treatment approaches. Among animal models of tuberculosis, our laboratory focuses primarily on the guinea pig model, which most accurately reflects the pathology of human patients with active tuberculosis. This model is currently being studied to better understand the mechanisms by which diabetes increases the risk of developing active tuberculosis disease, a comorbidity of emerging importance, especially in countries where tuberculosis is endemic. In conjunction with the laboratory of Dr. Randall Basaraba, we have developed the first guinea pig model of type 2 diabetes and diabetes-tuberculosis comorbidity. Our findings indicate that both metabolic and immunologic disturbances associated with diabetes may influence the susceptibility to tuberculosis, and that metabolic disease is also a feature of tuberculosis, even in the absence of diabetes. Our current research aims to better define the metabolic homeostasis and immunological mechanisms that may contribute to more severe tuberculosis disease in diabetics, in order to improve host immunity and identify adjunctive treatments for improving the response to antimicrobial therapy in the presence of comorbidities such as diabetes. Our findings from animal models are being translated to human TB patients and also applied to other diseases with autoimmune pathogenesis, including type 1 diabetes, as well as other models of diabetes-associated infection.

Dr. Richard Slayden
richard.slayden@colostate.edu | website

Dr. Richard Slayden has expertise in all stages of academic drug development ranging from basic bacterial physiology, target discovery and validation to development of drug delivery formulations and efficacy testing in animal models. He has been involved in M. tuberculosis research since 1993 and F. tularensis, B. pseudomallei and Y. pestis research since 2005. Uniquely, his work includes a wide variety of integrative research strategies that affords for a complete investigation of rug mode of action and bacterial metabolism and response in vivo. Specifically, his research team has experience indentifying clinically relevant drug targets, assessing protein function via gene dosage [knockout & knockdown mutants, dominant negative and merodiploid strains], determining mode of action, and advanced lead compound formulation development. Importantly, these strategies were developed to manipulate essential molecular targets and to exploit them for the development of novel broad-spectrum chemotherapies with potency against priority pathogens and medically important difficult to treat bacterial pathogens.

Dr. John S. Spencer
john.spencer@colostate.edu | website

With the support of an NIH/NIAID subcontract (HHSN201005160005 Mod 5, “Microbiology and Infectious Diseases Biological Resource Repository MID-BRR – CSU Subcontract”), our laboratory provides reagents derived from armadillo grown M. leprae bacilli used to produce whole cells, subcellular antigen fractions, carbohydrate and glycolipid molecules (such as lipoarabinomannan and the M. leprae-specific phenolic glycolipid, PGL-I), DNA, and E. coli-derived recombinant proteins to researchers all over the world, particularly where leprosy is endemic.

The recent completion of the genome sequences ofMycobacterium tuberculosis, M. leprae and other mycobacterial species provides a unique opportunity to study genomics, proteomics, metabolomics and host-pathogen interactions of these important human pathogens. Our research is focused on the following: 1) defining B and T cell epitopes of immunologically important proteins of M. leprae and M. tuberculosis that are recognized in animal infection models and human disease; 2) define disease-state-specific antigens of tuberculoid and lepromatous leprosy patients using ELISA, Western blot and protein/peptide microarray techniques; 3) identify recombinant proteins and/or peptides that can be combined to develop a simple in vitro blood test towards the early diagnosis of leprosy; 4) determine serological, cell mediated and transcriptional biomarkers of M. leprae infection and disease progression to identify those individuals most at risk for leprosy.

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