BBSP Faculty

How do networks of cells synchronize behaviors across differing spatial and temporal scales? This fundamental aspect of cellular dynamics is broadly relevant to understanding many biological systems in which the coherence of electrical or chemical signals is required for multicellular patterning or organ function. Our group’s primary research interests are related to understanding the cellular and microenvironmental conditions that are required to support the biorhythmic behavior of the system of cells that natively control heart rate, cardiac pacemaker cells. We utilize a variety of techniques including computational modeling, next generation sequencing, in vivo genetic manipulation, super-resolution imaging, and direct physiological recording to investigate the developmental processes that assemble the hearts pacemaking complex. The ultimate goals of these studies is to determine how the pacemaker cell lineage is patterned in the embryo, build strategies towards fabricating this cell type for therapeutic purposes, and identify vulnerabilities that may lead to pacemaker cell pathologies in humans.

Our lab is trying to understand the mechanisms by which long noncoding RNAs orchestrate the epigenetic control of gene expression. Relevant examples of this type of gene regulation occur in the case of X-chromosome inactivation and autosomal imprinting. We specialize in genomics, but rely a combination of techniques —  including genetics, proteomics, and molecular, cell and computational biology — to study these processes in both mouse and human stem and somatic cell systems.

We use cutting edge technology to study pathogenesis of human pulmonary diseases including cystic fibrosis, Job’s syndrome, idiopathic pulmonary fibrosis by both human specimens, mouse genetic models, with a goal of finding the therapies. Recently, we developed a serial of lung epithelial-lineage tracing systems, providing the powerful tools for identify mechanisms of lung disease involved in post-acute sequelae SARS-CoV-2 infection, also known as “long COVID”, in collaboration with Dr. Ralph Baric’s Lab at UNC-CH.

Males and females differ in their prelevance, treatment, and survival to a diverse set of human disease states. This is exemplified cardiovascular disease, a disease that takes more lives than all forms of cancer combined. In cardiac disease, women almost uniformly fare far worse than men: as of 2007 one woman dying for cardiovascular disease in the US every minute. Our lab focuses on sex disparities in development and disease. For these studies, we use a highly integrated approach that incorporates developmental, genetic, proteomic, biochemical and molecular-based studies in mouse and stem cells. Recent advances by our past students (presently at Harvard, John Hopkins and NIH) include studies that define the cellular and molecular events that lead to cardiac septation, those that explore cardiac interaction networks as determinants of transcriptional specificity, the mechanism and function of cardiac transcriptional repression networks, and the regulatory networks of cardiac sexual dimorphism. Our lab has opening for rotation and PhDs to study these rapidly emerging topics.

Our research focuses on the immunological aspects of pathogen-host interactions. The lab is actively involved in HIV pathogenesis and vaccine studies using the nonhuman primate model of SIV infection. We are particularly interested in pediatric HIV transmission by breast-feeding and the early, local host immune response. A main research focus is on developmental differences in host immune responses between infants and adults and how they alter pathogenesis. The effect of co-infections (e.g. malaria and Tb) on HIV pathogenesis and transmission is a second research focus. The lab is developing a nonhuman primate model of SIV-Plasmodium fragile co-infection to study HIV-P. falciparum infection in humans.

A major focus of the Diekman lab is to develop new strategies to limit age-related osteoarthritis (OA).  The lab uses genetically-engineered mouse models to investigate the development of cellular senescence in joint tissues with physiologic aging.  One goal of this work is to determine whether “senolytic” compounds that induce selective apoptosis in senescent cells will mitigate OA development.  Our group has also developed genome-editing protocols for primary human chondrocytes to produce single-cell derived colonies with homozygous knockout of target genes.  We are using engineered tissues from these cells to dissect the mechanism of genes implicated in OA development by genome-wide association studies, as well as coupling these technologies to high throughput screening approaches for OA drug discovery.

The Good Laboratory is focused on the cellular and molecular mechanisms involved in the pathogenesis of a devastating intestinal disease primarily affecting premature infants called necrotizing enterocolitis (NEC). The long-term goal of the Good Lab is to understand the signaling pathways regulating the uncontrolled immune response in NEC and how these responses can be prevented through dietary modifications or targeted intestinal epithelial therapies. Her basic and translational research utilizes a bench-to-bedside approach with multiple cutting-edge techniques. In her pre-clinical studies, their team utilizes a humanized neonatal mouse model of NEC to understand the signaling pathways and immune cell responses involved in NEC development. Specifically, the laboratory interrogates ways to modulate the immune response, epithelial cell and stem cell regeneration as well as early microbial colonization during NEC. In the clinical component of her research program, Dr. Good leads a large multi-center NEC biorepository for the dedicated pursuit of molecular indicators of disease and to gain greater pathophysiologic insights during NEC in humans. Dr. Good also developed a premature infant intestine-on-a-chip model to study NEC and provide a personalized medicine approach to test new therapeutics. Her laboratory is currently funded with multiple NIH R01 grants and has previously received K08 and R03 funding as well as awards from the March of Dimes, the Gerber Foundation and the NEC Society.

During cell shape change and motility, a dynamic cytoskeleton produces the force to initiate plasma membrane protrusion, while vesicle trafficking supplies phospholipids and membrane proteins to the expanding plasma membrane. Extracellular cues activate intracellular signaling pathways to elicit specific cell shape changes and motility responses through coordinated cytoskeletal dynamics and vesicle trafficking. In my lab we are investigating the role of two ubiquitin ligases, TRIM9 and TRIM67, in the cell shape changes that occur during neuronal development. We utilize a variety techniques including high resolution live cell microscopy, gene disruption, mouse models, and biochemistry to understand the complex coordination of cytoskeletal dynamics and membrane trafficking driving neuronal shape change and growth cone motility in primary neurons.

Imagine a naturally intelligent therapy that can seek out and destroy cancer cells like no other available treatment.  In the Hingtgen Lab, we are harnessing Nobel Prize-winning advancements to create a new type of anti-cancer treatment: personalized stem cell-based therapies.  We use a patient’s own skin sample and morph it into cells that chase down and kill cancer. We take advantage of a little-known aspect of stem cells- they can home in on cancer by picking up a signal through receptors on the cell surface. All the while, the therapeutic stem cells are pumping out potent anti-cancer drugs that selectively kill any cancer cell nearby while leaving the healthy brain unharmed. Our initial studies focused on aggressive brain cancers, however we quickly expanded our testing to a variety of cancer types. Working at the interface of basic science and human patient testing, our ultimate goal is to translate this novel approach into the clinical setting where it can re-define treatment for cancers that currently have no effective treatment options.

The McCauley Lab is interested in how the food we eat changes our physiology. Rare, nutrient sensing cells in the intestine called enteroendocrine cells secrete hormones in response to environmental cues that orchestrate systemic metabolism. How these cells regulate their neighbors in the gut is not well understood. We use mouse models which lack enteroendocrine cells and human pluripotent stem cell derived intestinal organoids to discover new roles for these master metabolic cells in the regulation of intestinal physiology and function. Enteroendocrine cells are dysregulated in inflammatory bowel disease, type 2 diabetes, and obesity, and loss of enteroendocrine cells results in malabsorptive diarrhea with poor survival. Our research has the potential to improve human health for a wide segment of the global population.

My laboratory research is focused on basic cell biology questions as they apply to clinical lung disease problems. Our main work recently has been contributing to the Cystic Fibrosis (CF) Foundtation Stem Cell Consortium, with a focus on developing cell and gene editing therapies for CF. I contribute to UNC team science efforts on cystic fibrosis, aerodigestive cancers, emerging infectious diseases and inhalation toxicology hazards. I direct a highly respected tissue procurement and cell culture Core providing primary human lung cells and other resources locally, nationally and internationally. I co-direct the Respiratory Block in the UNC Translational Educational Curriculum for medical students and also teach in several graduate level courses.

Interest areas: Developmental Biology, Cell Biology, Cancer Biology, Stem Cells, Genetics

PhD programs: Pathobiology & Translational Sciences, Genetics & Molecular Biology, Cell Biology & Physiology, Oral Biology, Biology

Tissue development and homeostasis depend on the precise coordination of self-renewal and differentiation programs. A critical point of regulation of this balance is at the level of cell division. In the Williams lab, we are interested in stratified epithelial development, stem cells, and cancer, with a particular interest in how oriented cell divisions contribute to these processes. Asymmetric cell divisions maintain a stable pool of stem cells that can be used to sustain tissue growth, or mobilized in response to injury. However, dysregulation of this machinery can lead to cancer, particularly in epithelia where tissue turnover is rapid and continuous. Using the mouse epidermis and oral epithelia as model systems, we utilize cell biological, developmental and genetic approaches to study the molecular control of oriented cell divisions and mitotic spindle positioning, and how division orientation impacts cell fate choices in development, homeostasis, injury, and disease.