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MTTs

The ITS facilitates translation of discoveries into practice by supporting Multidisciplinary Translational Teams (MTTs) – diverse groups of researchers advancing a specific translation to impact a variety of important health issues. Through this partnership, MTTs have access to the resources of the ITS and the CTSA consortium, allowing them to be even more effective in conducting collaborative research and mentoring trainees.

MTTs, regardless of their unique topic, all focus on translational projects and are composed of both senior and junior level investigators from multiple disciplines and departments. In conducting their research, MTTs also enhance collaboration among members and strengthen partnerships with other researchers, industry, and the community. In addition, the MTTs accelerate translation by securing extramural funding for their work and disseminating their research findings.

MTTs are led by an established Principal Investigator with national stature and track record of training. An Associate Director, typically an Assistant Professor or KL2 scholar, works in a real-world interprofessional environment to advance the MTT’s translational project. MTTs are expected to foster an opportunity for interprofessional training via providing role models, co-mentoring, and career development for the Associate Director and affiliated TL1 scholars. The MTT increases its capacity and innovation through publishing in scholarly journals, increasing its funding base, and participating in the ITS Leadership Community of Practice.



Collaborators:
Blake Rasmussen (PI) | Elena Volpi | Elizabeth Lyons | Gulshan Sharma | Blake B. Rasmussen (PI) | Melinda Sheffield-Moore | Soham Al Snih | Christopher Fry | Paula Skinkis | Shawn Goodlett | Eloisa Martinez | Roxana Hirst | Rachel Deer | Tatiana Moro | Ted Graber | Elfego Galvan | Rebecca Galloway | Roberto Garofalo | Edgar Dillon | Bill Durham | Craig Porter | Celeste Finnerty | Demi Tuvdendorj | Nisha Garg | Doug Paddon-Jones | Emily Lantz | Sanjeev Choudhary | Steve Fisher | James Goodwin | Elizabeth Protas | Rebeca Wong | Kenneth Ottenbacher

Summary: Loss of lean body mass and decreasing muscle strength are significant contributing factors to decline in function and loss of independence in older adults. UTMB is recognized nationally for research related to muscle biology and protein metabolism. For the past nine years research on aging muscle has been conducted by investigators supported by an Older Americans Independence (Pepper) Center grant from the NIA (P30AG024832, J. Goodwin, PI) and a series or R01s (R01AG16738, K. Ottenbacher, PI; R01HD0518441 E. Protas, PI; R01AR049877, B. Rasmussen, PI; and R01AG018311, R03AG023215, E. Volpi, PI). We have developed a comprehensive understand of the role of essential amino acids and exercise in muscle metabolism and protein synthesis in healthy older adults. Our research team is now ready to begin translating these findings by developing and testing interventions in clinical populations. Conducting trials in patient populations is a new area of investigation of the aging muscle research team.

The goal of this MTT is to develop and test interventions to improve function and independence in older adults.

Objectives/Milestones:

  • Identify functional outcome measures sensitive to change in muscle function and related to improved independence in older adults;
  • Develop sampling plans and recruitment strategies to obtain large samples of patients experiencing acute hospitalization and at risk for loss of independence;
  • Establish protocols and designs to conduct rigorous clinical trials using hospitalized patients and older persons living in the community.
Train doctoral students, postdoctoral fellows and K12 trainees in the data collection and analysis methods appropriate for conducting clinical trials in older adults.

Collaborators:
David Herndon (PI) | Celeste Finnerty | Michele Carter | Ludwik Branski | Hongjie Duan | Carlos Jimenez | Linda Sousse | William Norbury | Craig Porter | Oscar Suman | Heidi Spratt | Andrzej Kudlicki | Jong Lee | Bruce Luxon | Hyunsu Ju | Suresh Bhavnani | Kristofer Jennings | Ravi Radhakrishnan | Tracy Toliver-Kinsky | Clark Andersen | Arham Ali | Andrew Childress | Amina El Ayadi | Bernard Fongang | Ashley Guillory | Xueling Li | Jessica Tanksley | Manish Saraf | Jamie Bohanon | Mohammed Jamaluddin | Michael Wetzel | Sharon Best

Summary: The MTT in burns injury addresses several translational aspects in burn injury/response. First, although significant improvements in burns management has resulted in a reduction in mortality to less than 10%, early identification of those at risk for multiorgan failure, or mortality is needed. Severe burns in humans produces a catabolic state that persists throughout the first year after burn. This state is mediated by an increase in catecholamine production, resulting in lipolysis, muscle wasting, reduced lean body mass and depressed immune response. Propranolol administration has been shown to reduce hypermetabolism, increase lean body mass and improve immune function. About 10% of patients do not respond to propranolol for unknown reasons. In this MTT, CTSA resources will allow the identification of multiorgan failure and mortality, enabling the Shriner Burns Hospital to be a site for a phase III multicenter trial in propranolol administration in burns outcome.

Collaborators:  Donald Prough (PI) | Rinat Esenaliev (Co-I) 

Collaborators:
Midoro-Horiuti, Terumi (PI) | Choudhury, Barun | Goldblum, Randall | Ho, Shuk-mei | Kaphalia, Bhupendra | Murakami, Youko | Saade, George | Watson, Cheryl

Summary: Expanding upon established programs for studying the influences of environmental agents on the development of asthma, this project will build a multidisciplinary team of scientists with varied expertise in child asthma, environment toxicology, experimental endocrinology and toxicological chemistry to study environmental contributions to childhood asthma.

The long-term goal of this research is to elucidate the role of environmental estrogens, such as bisphenol A (BPA), in the development of asthma and other allergic diseases. The general approach is to identify epigenetic, cellular and functional biomarkers of BPA exposure that represent immunologic precursors of asthma in groups of infants with high and low concentrations of BPA in their cord blood serum. The study will identify biomarkers of fetal exposure of BPA that relate to the propensity to develop asthma. Answering this question will form the basis for future studies in which the relationship between selected biomarkers and the prevalence of asthma will be investigated in an expanded cohort study.

Collaborators:

David H. Walker (PI) |  Kimberly Schuenke | Rong Fang | Allan R. Brasier | Yingxin Zhao | Michael Loeffelholz | Jere W. McBride | Lucas S. Blanton | Juan P. Olano | Yuriy Fofanov | Jai Rudra | Richard Willson | Natalie Williams-Bouyer | Juan D Rodas | Rita de Sousa | Cecilia Y Kato | Sanjeev Kumar Sahni | Hema Narra | Tetyana Buzhdygan | Claire Smalley | Marylin Eliseyev | Hidalgo Diaz

Summary: The goal of our team is to establish highly specific and sensitive diagnostic assays at the early stage of infectious diseases caused by Rickettsia, Ehrlichia and Orientia, which are urgently needed for effective control of these diseases. We have identified the specific peptides that circulate in the blood of infected animal models based on affinity enrichment- mass spectrometry method (IP-SRM or IP-PRM). We plan to detect these specific peptides using monoclonal antibodies in human samples after development into a Lateral Flow Assay using glow-in-the-dark nanoparticles as reporters with high sensitivity and specificity. This MTT will bring together basic and clinical scientists to develop tests that can be used as point-of care diagnostic tests in clinics.

Collaborators:
Mark Hellmich (PI) | Csaba Szabo | Celia Chao | Katalin Modis | Bartosz Szczesny | Iryna Pinchuk | Steven Widen | John Zatarain | Ketan Thanki | Manjit Maskey | Mike Nicholls | ChesN'que Phillips | Romain Villeger | Tom Wood | Suimin Qiu

Summary: In the United States, an estimated 51,000 people (3,400 Texans) will die from metastatic colorectal cancer (mCRC) annually making it the third leading cause of cancer death for all ages [Siegel et al., Cancer J. Clin. 63:11, 2013]. Although, multi-agent systemic therapies have improved median patient survival in the last decade from < 1 year to approximately 2 years, only about half of all patients with mCRC respond to the current frontline (best-practice) therapies. Therefore, there is a critical need to discover and implement novel treatment for advanced disease. The ultimate goal of our multidisciplinary translational team (MTT) is to advance a new therapeutic concept to the stage of clinical use, in order to improve the quality of life and extend the survival of patients with metastatic gastrointestinal cancers.

Our research seeks to translate our basic understanding of tumor cell CBS and H2S production into novel therapeutic strategies for treating patients with mCRC. There are two arms to our approach. First, we will evaluate the anti-tumor efficacy of the CBS inhibitor aminooxyacetic acid (AOAA) either alone, or in combination best-practice therapies or FDA approved drugs that synergize with AOAA. Second, we will expand the scientific/conceptual foundations, as well as establish the interdisciplinary infrastructure necessary to initiate clinical trials to test the efficacy of AOAA and AOAA analogs in patients with mCRC, either as a monotherapy or in combination with current best-practice strategies.

Collaborators:
Steven Cohn (PI) | Jose Aguirre | Werner Braun | William Calhoun | Glenda Blaskey | Barun Choudhury | Yingzi Cong | Sharon Croisant | Sara Dann-Grice | Tonyia Eaves-Pyles | Aakash Gajjar | Xuan-Zheng Shi | Kristofer Jennings | Cheryl Juneau | Qingjie Li | Michael Loeffelholz | Gurinder Luthra | Lisa Nemeth | Alex-giovanny Peniche-trujillo | Iryna Pinchuk | Don Powell | Victor Reyes | Jai Rudra | Sushil Sarna | Pomila Singh | Xuan-Zheng Shi | Easwaran Variyam | John Wiktorowicz | John Winston

Summary:  The Gut Inflammation MTT investigates both C. difficile infection and inflammatory bowel disease. Notably, it has established IP-6 as a therapeutic candidate for C. diff infection, and it has provided important epidemiologic knowledge of risk factors. Aligned with its interests in C. diff epidemiology and pathophysiology, as well as IBD pathophysiology and clinical trials, it aims to:
1) Integrate translational studies of gut inflammation with clinical activities.
2) Initiate and participate in clinical trials.
3) Establish an IBD patient registry.
4) Establish a Gut Inflammation human tissue acquisition system and repository.

Collaborators: Elferink, Kees (PI) |  Ansari, Shakeel |  Brasier, Allan |  Calhoun, William |  Cicalese, Luca |  Denner, Larry |  Hossain, Ekram |  McKinney, Bernadette |  Merwat, Shahzad |  Montalbano, Mauro |  Petersen, John |  Spratt, Heidi |  Stevenson, Heather |  Utay, Netanya

Summary: We are working to identify and develop a highly sensitive and specific serum-based assay for early Hepatocellular Carcinoma (HCC) detection in the high-risk population, utilizing the unique and diverse resources present at UTMB to improve the diagnosis and treatment of liver cancer.

Liver cancer typically identified as HCC, is amongst the most common malignancies worldwide. HCC and accompanying mortality is increasing in the United States with an estimated 21,370 new cases in 2008, and 18,410 deaths. This comes at a time when mortality from most other solid tumors is decreasing. The anticipated continued rise in new HCC cases is due mainly to latent Hepatitis C virus (HCV) infection in the general population with the onset of HCC coming several decades after initial infection. The poor prognosis associated with HCC is primarily due to the diagnosis occurring at a late stage severely limiting effective therapeutic intervention. By contrast, early detection of HCC provides a number of potentially curative treatment options. Unfortunately, existing screening strategies to detect HCC in its early stages lack sensitivity and accuracy, or are risky and expensive. Therefore, surveillance of patients at highest risk for developing HCC, notably patients with cirrhosis, will benefit from new screening modalities based on reliable serum biomarkers capable of accurately detecting HCC in its earliest stages.

 GOALS

  1. To identify candidate serum biomarkers capable of identifying HCC.
  2. To validate the biomarkers in early HCC detection and in monitoring therapeutic efficacy following cancer treatment.

Collaborators:
Cunningham, Kathryn (P) | Anastasio, Noelle | Garcia, Maria | Gilbertson, Scott | Harvey, Edythe | Hommel, Jonathan | Jordan, Marcy | Kasper, James | Kuo, Yong-fang | Le, Donna | Moeller, F. Gerald | Nowakowski, Sara | Price, Amanda | Scott, Lauren | Sowers, Lawrence | Temple, Jeff | Thomas, Christopher | Wooten, Kevin | Zhou, Jia

Summary: The overarching goal of this MTT is to develop the best practices of translational research and employ these to discover new biomarkers and therapeutic approaches to the addictions and impulse control disorders. Building on our core strengths in cellular and animal models, clinical science, and chemistry, this MTT is addressing the fundamental gap between the genes, biology and impulsivity which underlies a spectrum of health maladies. Impulsivity or “action without reflection” is an endophenotype for the addictions, aggression/violence and obesity/binge eating disorders, conditions that together account for an incredible portion of the chronic disease burden in the U.S.

We are building on our prior studies that serotonin (5-HT) transmission, particularly through its cognate 5-HT2A receptor (5-HT2AR) and 5-HT2CR proteins, plays a key role in inherent levels of impulsivity, and explore the specific linkage between the biology of the 5-HT2AR/5-HT2CR systems and impulsivity in humans. Our overarching hypothesis is that high tonic/constitutive 5-HT2AR function and low tonic/constitutive 5-HT2CR function are drivers of high impulsivity. To test this hypothesis, we will develop a human subjects laboratory (Specific Aim 1) at UTMB to clinically (Barratt Impulsivity Scale; BIS-11) and experimentally analyze impulsivity in three behavioral tasks (Go/No-Go task, reversal learning task, reward-word Stroop task). We will recruit healthy human subjects (18-55 yr), collect blood samples and evaluate clinical and behavioral laboratory measures of impulsivity as well as subject history information on addiction, violence and eating behavior.

Collaborators:

Peter Melby (PI) |  Alejandro Castellanos | A. Clinton White | Miguel Cabada | Bruno Travi | Omar Saldarriaga | Andres (Willy) Lescano | Matthew Dacso |

Summary: The impact of neglected parasitic diseases on human health is staggering.  These chronic infections collectively affect more than a billion of the world’s poorest people (the so-called “bottom billion”), causing chronic disability, impaired development in children and reduced economic capacity in adults. Despite the huge burden of these diseases, research into their diagnosis, treatment, and prevention has been relatively neglected. To reduce the impact of these diseases in endemic resource-limited countries, it is imperative to develop low-cost, field-applicable diagnostic tests, especially tests that can be used at the point-of-care (POC). Our MTT will bring together basic, clinical, and epidemiologic scientists to develop for the first time RPA-based assays coupled with lateral flow detection for point-of-care diagnosis of selected intestinal protozoa, intestinal helminths, Leishmania, and Trypanosoma cruzi. 

In Specific Aim 1 we will focus on Fasciola and Strongyloides, two intestinal helminths of global importance. In Specific Aim 2 we will focus on a multiplex diagnostic test for the intestinal protozoa, Cryptosporidium, Giardia, and Entamoeba histolytica. In Specific Aim 3 we will develop diagnostic tests for cutaneous, mucosal and visceral leishmaniasis. In Specific Aim 4 we will focus on Trypanosoma cruzi, the cause of Chagas disease. In parallel with the laboratory based studies, we will work with epidemiologists to design a rigorous prospective field evaluation trial for each of the individual or multiplexed RPA-lateral flow strip diagnostic tests. We expect to provide two major deliverables: 1) a clinically-validated RPA-lateral flow diagnostic test for each proposed parasitic disease, ready for full-scale field evaluation, and 2) a rigorously designed study protocol for field evaluation of each of the RPA-lateral flow diagnostic tests that will form the basis of future proposals for extramural funding.

Collaborators:
Abate, Nicola (PI) | Belalcazar, Maria L. | Brasier, Allan | Bytautiene, Egle | Calhoun, William | Choudhary, Sanjeev | Denner, Larry | Finnerty, Celeste | Gomez, Guillermo | Herndon, David | Hommel, Jonathan | Jiang, Yongquan | Kasper, James | Makhlouf, Michel | McCue, David | Mitchell, Cindy | Motamedi, Massoud | Nemeth-Sweeney, Lisa | Olson, Gayle | Porter, Craig | Powell, Don | Saade, George | Sallam, Hanaa | Taglialatela, Guilio | Tilton, Ronald | Tumurbaatar, Batbayar | Tuvdendorj, Demidmaa | Vargas, Gracie | Vincent, Kathleen

Summary: Obesity is considered the driving force behind the growing epidemic of type 2 diabetes and cardiovascular disease in the US population. Clinical efforts to identify patients with obesity that are at risk for developing type 2 diabetes and cardiovascular disease have lead to the definition of the Metabolic Syndrome in the NCEP ATP III guidelines, in 2002. However, only approximately 1/3 (25%) of the overweight/obese population develops the metabolic syndrome and only 1/3 (8%) of the metabolic syndrome patients develop type 2 diabetes with increased risk for cardiovascular disease. On the other hand, it has become apparent that persons with low BMI and even with low waist circumference may be at risk for developing diabetes and cardiovascular disease. The limitation of the current definition of the metabolic syndrome in identifying patients at risk is even more evident in ethnic minorities. For example, for any degree of obesity and fat distribution Asian and Hispanics appear to be more susceptible to type 2 diabetes when compared to Whites of European descent. This observation could be explained on the basis of ethnic diversity in adipose tissue function and its ability to provide metabolic balance in conditions of excessive caloric intake. Our MTT will focus on identification of metabolic and genetic markers of adipose tissue dysfunction that may predict susceptibility to type 2 diabetes and its complications across all ethnic groups, independently of fat mass and distribution. Study subjects will be identified in the UTMB outpatient service clinics. Biomarkers will be identified looking at adipose tissue microarrays and proteomic analysis of adipose tissue samples for the diabetes risk, and looking at proteomic analysis of urine specimens for the diabetic complications. Inflammatory biomarkers will be major, but not exclusive, candidate for evaluation. Once these biomarkers are identified, a series of clinical and mechanistic studies will study specific pathways that are involved in the pathogenesis of insulin resistance, beta-cell dysfunction and retinal/renal abnormalities of these patients. This work will include metabolic patient-oriented research and also studies in cell and animal models to confirm mechanistic relevance of findings in association studies. Since it has recently become evident that aggressive glycemic control increases risk for mortality in patients with type 2 diabetes, we will develop intervention studies using both medical and metabolic surgery approaches to accomplish resolution of adipose tissue dysfunction as preferable approach to prevent type 2 diabetes and its complications. Surgical intervention with whole pancreas or islet cell transplantation will be evaluated for its effectiveness in improving adipose tissue function and risk for progression of diabetes complications.

Collaborators:
Jacques Baillargeon (PI) | Yong-Fang Kuo | Gulshan Sharma | Mohammed Zaidan | Nai-Wei Chen

Summary: Currently, this team aims to understand the role of testosterone therapy in treating COPD and depression.

Collaborators: Garofalo, Roberto (PI) | Ansar, Maria | Bao, Xiaoyong | Brasier, Allan | Casola, Antonella | Chambliss, Jeffrey | Gupta, Meera | Ivanciuc, Teodora | Rajarathnam, Krishna | Rodrigues, Lilia | Tribble, Cynthia

Summary: Bronchiolitis, the major cause of hospitalization in the first year of life is primarily caused by respiratory syncytial virus (RSV) infections. Exposure to second hand tobacco smoke (SHTS) occurs in up to 60% of the infants with RSV bronchiolitis in the US, and different studies have suggested that SHTS is a risk factor for the development of severe RSV infection. Oxidative stress response in the airways plays a major role in the pathogenesis of severe RSV bronchiolitis particularly if the process is enhanced by the exposure to pro-oxidative toxicants such as tobacco smoke.

Areas of investigation

  1. Biomarkers and predictors of viral bronchiolitis and pneumonia
  2. Innate immune response in the lung
  3. Oxidative injury, antioxidant gene regulation and gene polymorphism
  4. Second hand tobacco smoke exposure as co-factor

Collaborators:
Calhoun, William (PI) | Ameredes, Bill | Brasier, Allan | Crowder, Jerome | Kurosky, Alexander | McKinney, Bernadette | Pazdrak, Konrad | Spratt, Heidi | Veeranki, Sreenivas | Wiktorowicz, John

Summary: Although patients with severe asthma constitute only 5-10% of all patients with the disease, this small subgroup accounts for a disproportionate share of morbidity and medical costs. Severe asthma is a syndrome that is characterized by a relative lack of responsiveness to gluocorticoids. It is clear that this group is heterogenous in nature, yet objective methods for identification of those at risk are not available. Seeks to identify protein patterns that are associated with asthma severity or its complications to improve the ability to phenotype subjects with asthma. New technologies are used to measure inflammation using optical and proteomics technologies. This MTT interfaces with multicenter studies, including the US Severe Asthma Research Program (SARP), Asthma Clinical Research Network (ACRN), and the NHLBI Proteomics Center, as well as with an NIAID - funded P01 entitled, Signaling in Airway Inflammation.

Objectives/Milestones:

  1. Recruit normal volunteers to establish a reference dataset of normal BAL proteins;
  2. Create integrated clinical and proteomic database for severe asthma data management;
  3. Develop web based data capture forms for conducting clinical studies at UTMB and its clinics;
  4. Develop and validate a novel biomarker discovery platform for identification of proteomic signatures in bronchoalveolar lavage;
  5. Validate models for pattern recognition using cytokine patterns in an independent subject group;
  6. Compete for K-level NIH funding, and a multi-investigator R01 project.
Collaborators:
Berenson, Abbey | Barrett, Alan | Hirth, Jacqueline | Kuo, Yang-fang | Morgado, Margarita | Rodriguez, Ana | Rojahn, Susan | Rupp, Richard

Summary:The reproductive period comprises 35 years of a woman’s life. During this time, women experience an evolving spectrum of physiological and psychosocial issues that may affect their health. UTMB is a leader in research on women’s health, including promotion and prevention, including pregnancy, contraception, skeletal health, and health risk behaviors. Our team’s research focuses on minority women of low socio-economic status, and has led to the development of several clinical interventions. We represent various schools, disciplines, and departments, highlighting our historical strengths in translational research among clinical and community populations. Our unique group has representation from obstetrics/gynecology, nursing, psychology, epidemiology, family medicine, and statistics. We are testing several new interventions. One is an educational and behavioral intervention designed to increase the consistency and correctness of oral contraceptive use among new users 16-24 years of age. Another intervention involves how nurses inform women that they have an abnormal Pap smear result. This culturally sensitive intervention is designed to increase the number of women who report to clinic for further evaluation after being informed of an abnormal Pap smear. New projects will include developing a weight loss intervention during the postpartum period and assessment of health risk behaviors among adolescent women. The broad goal of this MTT is to develop and test interventions to improve health outcomes in reproductive-aged women, which will influence their health status in later years.

Currently, this team focuses on cervical cancer prevention via HPV vaccination, and through its CPRIT-funded vaccination program, it has improved community awareness of HPV vaccination and cancer prevention measure among community members, improved HPV vaccination rates, and reduced the burden on clinicians to determine vaccination status and remind patients to follow up for additional doses. 

Objectives/Milestones:

  1. Expand our knowledge base of the health needs, risk and protective factors, and culturally sensitive health interventions among underserved women, with a particular focus on Hispanics
  2. Conduct focus groups and qualitative surveys to investigate determinants of health behaviors among underserved women of reproductive age.
  3. Develop, pilot test, and refine a battery of measures that integrates objective physiological and psychosocial outcome data (e.g., assays of relevant biomarkers, bone density tests, blood pressure, self-report of social support, stress, depressive symptoms, and body image) that we will apply to a broad range of studies. For example, a study of more than 800 women using one of three contraceptive methods will measure bone mineral density, serum lipids, and depressive symptoms
  4. Test, adapt, or modify existing health behavior interventions to address significant barriers to and facilitators of healthy practices specific to our multiethnic population, and ensure sustainability of the interventions.
  5. Train T32 postdoctoral fellows, K12 scholars, and junior faculty in methods appropriate for conducting clinical research in multiethnic cohorts of reproductive-aged women.
Collaborators: Tim Reistetter (PI) 

Summary: This MTT plans to develop a chronic disease self management program for community-dwelling stroke survivors. This program is predicted to increase survivors' community participation and decrease hospital readmissions. This approach, if successful, can then be applied to other patient populations beyond stroke. To date, this MTT has developed customizable self management plans for different comorbidity clusters, and it is now focused on protocol development for the chronic disease self management program.

Collaborators:
Douglas Tyler (PI) | Paul Dolber | Kelly Olino | Jennifer Perone | Iryna Pinchuk | Heidi Spratt | Suimmin Qiu | Celia Chao | David Herndon | Celeste Finnerty | Harold Hawkins | Yingzi Cong | Avi Markowitz | Tracy Toliver | Fujio Suzuki | Lynn Soong | Jai Rudra | Jianli Dong

Summary: None yet

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