The Kunisaki lab is a NIH-funded regenerative medicine group within the Division of General Pediatric Surgery at Johns Hopkins that works at the interface of stem cells, mechanobiology, and materials science. We seek to understand how biomaterials and mechanical forces affect developing tissues relevant to pediatric surgical disorders. To accomplish these aims, we take a developmental biology approach using induced pluripotent stem cells and other progenitor cell populations to understand the cellular and molecular mechanisms by which fetal organs develop in disease.

Our lab projects can be broadly divided into three major areas: 1) fetal spinal cord regeneration 2) fetal lung development 3) esophageal regeneration

Lab members: Juan Biancotti, PhD (Instructor/lab manager); Annie Sescleifer, MD (postdoc surgical resident); Kyra Halbert-Elliott (med student), Ciaran Bubb (undergrad)

Recent publications:
Kunisaki SM, Jiang G, Biancotti JC, Ho KKY, Dye BR, Liu AP, Spence JR. Human induced pluripotent stem cell-derived lung organoids in an ex vivo model of congenital diaphragmatic hernia fetal lung. Stem Cells Translational Medicine 2021, PMID: 32949227

Biancotti JC, Walker KA, Jiang G, Di Bernardo J, Shea LD, Kunisaki SM. Hydrogel and neural progenitor cell delivery supports organotypic fetal spinal cord development in an ex vivo model of prenatal spina bifida repair. Journal of Tissue Engineering 2020, PMID: 32782773.

Kunisaki SM. Amniotic fluid stem cells for the treatment of surgical disorders in the fetus and neonate. Stem Cells Translational Medicine 2018, 7:767-773

The O’Rourke Lab uses an integrated approach to study the biophysics and physiology of cardiac cells in normal and diseased states. Research in our lab has incorporated mitochondrial energetics, Ca2+ dynamics, and electrophysiology to provide tools for studying how defective function of one component of the cell can lead to catastrophic effects on whole cell and whole organ function. By understanding the links between Ca2+, electrical excitability and energy production, we hope to understand the cellular basis of cardiac arrhythmias, ischemia-reperfusion injury, and sudden death. We use state-of-the-art techniques, including single-channel and whole-cell patch clamp, microfluorimetry, conventional and two-photon fluorescence imaging, and molecular biology to study the structure and function of single proteins to the intact muscle. Experimental results are compared with simulations of computational models in order to understand the findings in the context of the system as a whole. Ongoing studies in our lab are focused on identifying the specific molecular targets modified by oxidative or ischemic stress and how they affect mitochondrial and whole heart function. The motivation for all of the work is to understand • how the molecular details of the heart cell work together to maintain function and • how the synchronization of the parts can go wrong Rational strategies can then be devised to correct dysfunction during the progression of disease through a comprehensive understanding of basic mechanisms. Brian O’Rourke, PhD, is a professor in the Division of Cardiology and Vice Chair of Basic and Translational Research, Department of Medicine, at the Johns Hopkins University.

The Foster Lab uses the tools of protein biochemistry and proteomics to tackle fundamental problems in the fields of cardiac preconditioning and heart failure. Protein networks are perturbed in heart disease in a manner that correlates only weakly with changes in mRNA transcripts. Moreover, proteomic techniques afford the systematic assessment of post-translational modifications that regulate the activity of proteins responsible for every aspect of heart function from electrical excitation to contraction and metabolism. Understanding the status of protein networks in the diseased state is, therefore, key to discovering new therapies. D. Brian Foster, Ph.D., is an assistant professor of medicine in the division of cardiology, and serves as Director of the Laboratory of Cardiovascular Biochemistry at the Johns Hopkins University School of Medicine.

The Pathak lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. We develop novel imaging methods, computational models and visualization tools to ‘make visible’ critical aspects of cancer, stroke and neurobiology. Our research broadly encompasses the following areas: Functional and Molecular Imaging; Clinical Biomarker Development; Image-based Systems Biology and Visualization and Computational Tools. We are dedicated to mentoring the next generation of imagers, biomedical engineers and visualizers. Additional information can be found at www.pathaklab.org or by emailing Dr. Pathak.

The Johns Hopkins Center for Global NCD Research and Training consists of faculty, fellows, and students from institutions across the United States and around the globe. Our mission is to conduct high-quality research and training for the prevention and control of non-communicable diseases in low- and middle-income countries (LMIC), with an aim to build local capacity through partnerships with local institutions and communities. Our current projects encompass subject matters ranging from clean cookstoves to mental health and involve sites in Peru, Uganda, Nepal, and Bangladesh. The burden of NCDs in LMICs is growing rapidly as a result of population aging, rapid unplanned urbanization, and the globalization of unhealthy lifestyles. We envision a robust and sustainable community of NCD researchers and trainees in both high and low income settings dedicated to improving health and well-being for all.

The Barouch Lab is focused on defining the peripheral cardiovascular effects of the adipocytokine leptin, which is a key to the understanding of obesity-related cardiovascular disease. Interestingly, many of the hormonal abnormalities seen in obesity are mimicked in heart failure. The research program will enhance the understanding of metabolic signaling in the heart, including the effects of leptin, exercise, sex hormones, and downstream signaling pathways on metabolism and cardiovascular function. The lab also is working to determine the precise role of the “metabolic” beta-3 adrenergic receptor (ß3AR) in the heart and define the extent of its protective effect in obesity and in heart failure, including its role in maintaining nitric oxide synthase (NOS) coupling. Ultimately, this work will enable the exploration of a possible therapeutic role of ß3AR agonists and re-coupling of NOS in preventing adverse ventricular remodeling in obesity and in heart failure. Lili Barouch, MD, is an associate professor of medicine in the Division of Cardiology and a member of the Advanced Heart Failure and Cardiac Transplantation group at the Johns Hopkins University School of Medicine.

The Arking Lab studies the genomics of complex human disease, with the primary goal of identifying and characterizing genetics variants that modify risk for human disease. The group has pioneered the use of genome-wide association studies (GWAS), which allow for an unbiased screen of virtually all common genetic variants in the genome. The lab is currently developing improved GWAS methodology, as well as exploring the integration of additional genome level data (RNA expression, DNA methylation, protein expression) to improve the power to identify specific genetic influences of disease. The Arking Lab is actively involved in researching: • autism, a childhood neuropsychiatric disorder • cardiovascular genomics, with a focus on electrophysiology and sudden cardiac death (SCD) • electrophysiology is the study of the flow of ions in biological tissues Dan E. Arking, PhD, is an associate professor at the McKusick-Nathans Institute of Genetic Medicine and Department of Medicine, Division of Cardiology, Johns Hopkins University.

Dr. Atta and his research team explore the epidemiological and clinical interventions of a variety of kidney diseases. Our goal is not only to advance the understanding of many kidney diseases but also to capitalize on novel discoveries of basic science to treat a wide range of rare and common kidney disorders.

• Multi-international observational study of a rare form of amyloid (LECT2 amyloid) to understand its natural history with the ultimate interest of treating this condition.
• Our group has launched a project investigating the impact of COVID19 on the kidney to identify risk factors influencing outcome across different clinical phenotypes
• In collaboration with the Division of Infectious Diseases and the School of Public Health, our research has focused on the epidemiology of HIV and kidney disease. We also study clinical markers and contributing factors in the progression of kidney disease, and the association between kidney disease and heart disease.
• Our research group is participating in a multicenter consortium serving as a clinical core site to study the pathogenesis of HIV-associated kidney disease by providing well-characterized clinical specimens and corresponding clinical and laboratory data.

The Penet lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The lab research focuses on using multimodal imaging techniques to better understand the microenvironment and improve cancer early detection, especially in ovarian cancer. By combining MRI, MRS and optical imaging, we are studying the tumor microenvironment to understand the role of hypoxia, tumor vascularization, macromolecular transport and tumor metabolism in tumor progression, metastasis and ascites formation in orthotopic models of cancer. We also are studying the role of tumor-associated macrophages in tumor progression.

The research conducted in the Mumm Lab (Dept. of Ophthalmology, Wilmer Eye Institute) is focused on understanding how neural circuits are formed, how they function, and how they can be regenerated, to develop new therapies for retinal regeneration. Toward that end, we investigate the development, function, and regeneration of disease-relevant neurons and neural circuits responsible for vision. An emphasis is placed on translating what can be learned in regenerative model systems to develop novel therapies for stimulating dormant regenerative capacities in humans, Therefore, we apply what we learn from a naturally regenerative species, the zebrafish, toward the development of novel therapies for restoring visual function to patients. We place an emphasis on unique perspectives zebrafish afford to biological studies, such as in vivo time-lapse imaging of cellular behaviors and cell-cell interactions, and high-throughput chemical and genetic screening. We have pioneered several technologies to support this work including multicolor imaging of neural circuit formation, a selective cell ablation methodology, and a quantitative high-throughput phenotypic screening platform. Together, these approaches are providing novel insights into how the degeneration and regeneration of discrete retinal cell types is controlled.