Our Multidisciplinary Translational Teams

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.

Leadership:
Blake Rasmussen (PI)

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. Since 2000, research on aging muscle has been conducted by investigators supported by a Claude D. Pepper Older Americans Independence Center(OAIC) grant from the NIA (P30AG024832, E. Volpi, PI). We have developed a comprehensive understanding of the role of essential amino acids and exercise in muscle metabolism and protein synthesis in healthy older adults. Our research team is beginning to translate 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.

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

Summary:
During gestation, labor and the immediate post-partum interval, the fetus and neonate undergo profound challenges to cerebral oxygenation. Fetal arterial oxygen saturation (SaO2) is ~ 30 - 60%, in contrast to 95-100% in healthy children. During labor, uterine contractions and maternal pushing reduce placental blood flow, while increases in uterine pressure and compression of the skull increase intracranial pressure, thereby limiting cerebral perfusion. After delivery, the neonatal cardiopulmonary system must rapidly transition to oxygenating and circulating blood. We hypothesize that even normal labor and delivery produce severe, intermittent cerebral ischemia that, under normal circumstances, appears to be compatible with subsequent normal neurologic development. There are currently no specific, accurate data that characterize fetal or neonatal cerebral circulatory adequacy. Fetal ECG monitoring, including ST segment analysis, correlates poorly with neurologic outcome. Neonatal near-infrared spectroscopy (NIRS) was unsuccessfully used to direct postpartum management, likely because of the well-established confounding variables associated with NIRS. We have assembled a multidisciplinary team -- neonatologists, maternal-fetal obstetricians, bioengineers and anesthesiologists -- that has applied unique optoacoustic technology, invented and developed at UTMB, to perform the first-ever studies of fetal cerebral circulation during labor and delivery. Specific measurement of oxygen saturation in the fetal and neonatal superior sagittal sinus (SsssO2) directly assesses the ability of cerebral oxygen delivery (cerebral blood flow X arterial oxygen content) to meet cerebral oxygen demand. We speculate that there are critical thresholds for the level and duration of SsssO2, beyond which brain injury is more likely. As a critical first step toward identifying those thresholds, we will characterize in apparently healthy fetuses and newborns the range of SsssO2 between and during contractions, the normal course of recovery of SsssO2 after contractions, the normal range of SsssO2 during Cesarean section and the normal course of changes in SaO2 and SsssO2 during the circulatory transition.

Leadership:
Terumi Midoro-Horiuti (PI)

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.

Leadership:
David H. Walker (PI) | Rong Fang (PM)

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.

Leadership:
Mark Hellmich (PI) | Celia Chao (PM)

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.

Leadership:
Steven Cohn (PI) | Sara Dann-Grice (PM)

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.

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.

Leadership:
Kathryn Cunningham (PI) | Jonathan Hommel (PM)

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.

Leadership:
Peter Melby (PI) | Alejandro Castellanos (PM)

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.

Leadership:
Jacques Baillargeon (PI)

Summary:
The overarching goal of the PCOR in Men’s Health Multidisciplinary Translational Team (MTT) is to conduct patient-centered research in Men’s Health, with particular emphasis on informing the development of randomized clinical trials (RCTs). Testosterone replacement therapy (TRT)—one of the most highly publicized and controversial issues in Men’s Health over the last decade—will be the focus of our MTT for the initial 2-year funding period. We believe that this topic is broadly representative of the many clinical, biological, and behavioral issues that underlie Men’s Health. Moreover, testosterone therapy is in critical need of rigorous patient-centered research to bring clarity to discordant treatment patterns, ambiguous diagnostic criteria, conflicting clinical practice guidelines, and highly variable patient perceptions of risks and benefits. Our MTT unifies expertise in PCOR, RCTs, Health Informatics, Community Engagement, Internal Medicine, Endocrinology, Pulmonology, and Rehabilitation Sciences around a common theme of Men’s Health. This MTT—launched in parallel to the UTMB Men’s Health Clinic—will provide a wide range of opportunities for the development of patient-centered translational research at UTMB, particularly the development of RCTs, patient registries, and ultimately the translation of our findings into clinical practice. Stakeholders (physician, patient, administrative) will play a critical role in all phases of this research—conceptual, design, analysis, and dissemination.

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

Leadership:
William Calhoun (PI)

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.

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.