Bone Pathobiology Our bone biology programs stimulate innovative, interdisciplinary approaches to identifying and characterizing key mechanisms in underlying bone loss and regeneration in skeletal and craniofacial development, and the regulation of these processes towards translational research. Major integrative research themes include: Cancer-associated bone pathologies Inflammatory bone loss Osteoporosis and osteopenia Rheumatoid arthritis Related Faculty: Xu Feng, Blake Hildreth, Joanne Murphy-Ullrich, Selvarangan Ponnazhagan, Gene Siegal, Yang Yang Cancer Biology Our internationally recognized cancer biologists and pathologists are involved in interdisciplinary and collaborative research covering a broad range of cancer-related topics. These include elucidating basic mechanism(s) underlying cancer development and metastasis, the role of the extracellular matrix and tumor microenvironment, genomics and metabolism, diagnostics and experimental therapeutics, translational studies, racial disparities and outcomes research. In addition, Department of Pathology faculty have: i) Developed UALCAN; an integrated data-mining platform to facilitate the comprehensive analysis of cancer transcriptome ii) Overseen the UAB Tissue Biorepository which collects, processes, stores, and distributes high quality human tissue specimens to investigators conductingcancer related research Department of Pathology Cancer Focus Areas: Breast Cancer Related Faculty: Scott Ballinger, Joanne Murphy-Ullrich, Selvarangan Ponnazhagan, Lalita Shevde-Samant, Rajeev Samant, Sooryanarayana Varambally Gynecologic and Genitourinary Cancer Related Faculty: Upender Manne, Mythreye Karthikeyan, Selvarangan Ponnazhagan, Sooryanarayana Varambally Gastrointestinal Cancer Related Faculty: William Grizzle, Upender Manne, George Netto, Sooryanarayana Varambally Hematological Cancers Related Faculty: Elizabeth Brown, Joanne Murphy-Ullrich, Ralph Sanderson, Yang Yang Neuro-oncology Related Faculty: Erin Eun-Young Ahn, C. Ryan Miller Health Disparity and Outcomes Research In Cancer Related Faculty: Elizabeth Brown, Upender Manne Cardiovascular and CardiometabolicDisease Research interests in cardiovascular disease are broad and include interests in understanding the role of bioenergetics, environmental stress, inflammation, nutrition and circadian rhythm, oxidative and reductive stress within the following disease areas Atherosclerosis and Vascular disease, Hypertension and Cardiomyopathy with a significant focus on how these diseases are impacted by Diabetes,Obesity and Liver disease. Related Faculty: Shannon Bailey, Scott Ballinger, John Chatham, Victor Darley-Usmar, Girish Melkani, Vivek Nanda, Rakesh Patel, Rajasekaran Namakkal-Soorappan, Adam Wende Computational Biology and Biomedical Data Sciences Our team of computational biologists, bioinformaticians, data scientists, software developers, and variant analysts are involved in basic, clinical and translational research and molecular diagnostics. As a multi-disciplinary team working in collaboration with experts here at UAB and around the world, we aim to help patients, the families, and those who take care of them. Computational Biology Our computational biology team develops and applies methods and algorithms aimed at identifying causal variants, molecular modifiers, pharmacogenomics loci, and molecular biomarkers using omics datasets and integrative computational analyses. We use these methods to identify the role of this variation in human health and disease. Data Science Our data science team implements machine learning approaches to more efficiently identify, classify, and interpret molecular variation associated with human disease. Data science approaches are being used to speed up and reduce the cost of interpretation, better classify variation, and study factors associated with genotype - phenotype associations. Software Development Our software development team develops commercial grade software to support all of our projects. A particular focus is on platforms for variant interpretation in both cancer and rare or undiagnosed disease. These tools have been used in a number of clinical laboratories to diagnose dozens of novel disorders. They have been used to diagnose many thousands of patients with genetic disorders including cancers. Variant Interpretation Our variant interpretation team performs variant analysis and interpretation on variation identified in a vast number of genetic diseases. These include essentially all rare diseases as well as more common diseases including cancers. We have aided in diagnosis of thousands of patients. Data repositories Making use of the components above we undertake a variety of data integration and knowledge generation projects including analysis of archival cases to identify new biomarkers import for the diagnosis, prognosis, and treatment of human malignancy. Related Faculty: Darshan Shimoga-Chandrashekar Related Links: Diabetes and Insulin Resistance Research interests in diabetes and insulin resistance include studies focused on altered cellular signaling in the context of both type 1 and type 2 diabetes, as well as the progression from obesity to pre-diabetes and the downstream consequences of each. Specific projects focus on the complications associated with diabetes in the context of cardiovascular and liver diseases with others in the division working at intersection of this and other pathologies (e.g. cancer biology) and the altered metabolic milieu that accompanies diabetes. Faculty: Shannon Bailey, Scott Ballinger, John Chatham, Victor Darley-Usmar,Girish Melkani, Vivek Nanda, Rakesh Patel, Rajasekaran Namakkal-Soorappan, Lalita Shevde-Samant, Adam Wende Fat Embolism Syndrome FES is a life-threatening condition that affects patients with hemoglobinopathies without pathognomonic signs or symptoms but very high mortality without red cell exchange. At UAB, we have learned to recognize these patients based on their common presentation of acute and severe back pain, respiratory or neurologic impairment, anemia and thrombocytopenia. We have also observed and reported the importance of early recognition and treatment with red cell exchange or transfusion. We are now trying to understand the pathogenesis of FES, how to avoid, and how to determine at-risk patients. Furthermore, through the literature and national and international presentations, we have strived to increase awareness of FES. Related Faculty: Marisa Marques, Jose Lima, Chad Siniard, Nirupama Singh Immunity, Immunology and Infectious Disease Our internationally-recognized immunologists and microbiologists are involved in basic, clinical and translational research with focus areas in T-cell and Neutrophil biology, and understanding their roles in modulating Gut Immunity and Infectious Diseases (including HIV and associated comorbidities). Additional areas of interest include understanding how the oral and gut microbiome modulate immunity and inflammatory disease and evaluation of commercial diagnostic tests and development of novel molecular assays to more accurately diagnose infectious diseases. Projects utilize patient samples and model systems to characterize and identify key mediators of microbial detection by the immune system, interaction with host cells, and virulence factors. Related Faculty: Robin Hatton, Zdenek Hel, Sixto Leal, Craig Maynard, Rakesh Patel, Casey Weaver Liver and Digestive Diseases Research projects in liver and digestive diseases are broad in scope and cover pre-clinical, translational, and clinical investigations in several areas, including alcohol-, obesity-, and diabetes-related liver disease; immune responses to gut microbiota in health and disease, including Crohn’s disease and ulcerative colitis; dysbiosis; HIV/ART-associated gut and liver injury; gastrointestinal, colorectal and pancreatobiliary cancers; mechanisms of fibrosis; and hepatic insulin resistance associated with trauma. Faculty: Sameer Al Diffalha, Shannon Bailey, Leona Council, Deepti Dhall, Robin Hatton, Zdenek Hel, Goo Lee, Upender Manne, Craig Maynard, and Casey Weaver. Neurodegenerative Diseases Areas of interest include understanding the cellular and molecular mechanisms responsible for autophagy and cell death in neurodegenerative diseases including Parkinsons. Additional areas of interest include understanding how altered T-cell function during gut inflammation may modulate the pathogenesis of neurodegenerative disease Related Faculty: Shu Chen, Jianhua Zhang Patient Management A multidisciplinary team, including transfusion medicine, has been working to improve the appropriateness of blood transfusions, also known as Patient Blood Management (PBM) at UAB since 2007. This effort has led to an overall decrease in the blood demand for the hospital by 25 percent, making UAB an international leader in PBM. Through better use of blood, we have avoided shortages and have blood available for patients with conditions such as massive hemorrhage, sickle cell disease, cancer, or treatment with drugs that prevent them from producing red blood cells. Our group studies how the culture change that allowed our PBM to be successful, has developed over time and adapted to the evolving needs of the patients treated at UAB. In addition, we are interested in the impact of the changes in patients’ outcomes as well as hospital technical labor and administrative costs. Related Faculty: Marisa Marques, Jose Lima, Chad Siniard, Nirupama Singh Redox biology and mitochondrial function Ongoing projects are focused on how perturbations in redox signaling lead to oxidative and/or reductive stress to cause inflammatory tissue injury. Our faculty have developed and implementing protocols that assess diverse redox mediators and their mechanisms of action with current areas of interest being reductive stress, metabolism and bioenergetics, mitochondrial genetics and mitochondrial based biomarkers, and interplay between redox signaling and protein glycosylation. Disease areas of focus include atherosclerosis, acute lung injury, liver disease, cancer, heart failure, and neurodegeneration. Faculty: Rakesh Patel, Shannon Bailey, Raj Namakkal Soorappan, Scott Ballinger, Jianhua Zhang, Victor Darley-Usmar, Adam Wende, John Chatham, Vivek Nanda, Girish Melkani, Mythreye Karthikeyan, Transfusion Medicine Evidence has accumulated that red blood cells have a narrow therapeutic benefit that has to be balanced against the risks caused by the storage lesion. Although not yet well-defined, it is clear that a number of biochemical changes take place in the bag which can help explain increased morbidity and mortality that correlates with volume of cells transfused, especially to trauma victims. Although most of our data are retrospective, we have ongoing research initiatives to expand our understanding of the effect of age of blood when given to trauma patients. More recently, these efforts have expanded to include the changes that occur in whole blood while stored in the Blood Bank. Ultimately, we are seeking to determine how in vitro changes may contribute to end-organ injury of trauma patients receiving massive transfusions. Related Faculty: Marisa Marques, Rakesh Patel