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

Epilepsy affects 1-3% of the population and can have a profound impact on general health, employment and quality of life. Medial temporal lobe epilepsy (MTLE) develops in some patients following head injury or repeated febrile seizures. Those affected may first suffer spontaneous seizures many years after the initial insult, indicating that the neural circuit undergoes a slow pathologic remodeling over the interim. There are currently no methods of preventing the development of MTLE. It is our goal to better understand the process in order to slow, halt, and ultimately reverse it. Our laboratory draws on electrophysiology, molecular biology, and morphology to study the contribution of dysregulated neurogenesis and newborn neuron connectivity to the development of MTLE. We build on basic research in stem cell biology, hippocampal development, and synaptic plasticity. We work closely with colleagues in the Institute for Cell Engineering, Neurology, Neurosurgery, Biomedical Engineering, and Radiology. As physician neuropathologists our grounding is in tissue alterations underlying human neurologic disease; using human iPSC-derived neurons and surgical specimens we focus on the pathophysiological processes as they occur in patients. By understanding changes in cell populations and morphologies that affect the circuit, and identifying pathologic alterations in gene expression that lead to the cell-level abnormalities, we hope to find treatment targets that can prevent the remodeling and break the feedback loop of abnormal activity > circuit change > abnormal activity.

The Robert Wise Lab conducts clinical trials to study chronic obstructive lung diseases (COPD). We investigate inhaled corticosteroids in patients with mild to moderate COPD and the effectiveness of anti-inflammatories in allowing lung growth in mild to moderate asthmatic children. Our research includes exploring the efficacy of various treatments for asthmatic women who are pregnant and of lung-volume reduction surgery for emphysema patients. We also conduct studies of the clinical epidemiology, pathobiology and treatment of interstitial lung disease in patients with scleroderma.

The mission of the Stroke Cognitive Outcomes and Recovery (S.C.O.R.E.) Lab is to enhance knowledge of brain mechanisms that allow people recover language, empathy, and other cognitive and communicative functions after stroke, and to improve ways to facilitate recovery of these functions after stroke. We also seek to improve the understanding of neurobiology of primary progressive aphasia., and how to enhance communication in people with this group of clinical syndromes.

The main research goals of my laboratory are: (1) to identify and study the biology of novel cancer selective targets whose enzymatic function can be exploited for therapeutic and diagnostic purposes; (2) to develop methods to target novel agents for activiation by these cancer selective targets while avoiding or minimizing systemic toxicity; (3) to develop novel agents for imaging cancer sites at earliest stages. To accomplish these objectives the lab has originally focused on the development of prodrugs or protoxins that are inactive when given systemically via the blood and only become activated by tumor or tissue specific proteases present within sites of tumor. Using this approach, we are developing therapies targeted for activation by the serine proteases prostate-specific antigen (PSA), human glandular kallikrein 2 (hK2) and fibroblast activation protein (FAP) as well as the membrane carboxypeptidase prostate-specific membrane antigen (PSMA). One such approach developed in the lab consists of a potent bacterial protoxin that we have reengineered to be selectively activated by PSA within the Prostate. This PSA-activated toxin is currently being tested clinically as treatment for men with recurrent prostate cancer following radiation therapy. In a related approach, a novel peptide-cytotoxin prodrug candidate that is activated by PSMA has been identified and is this prodrug candidate is now entering early phase clinical development. In addition, we have also identified a series of potent inhibitors of PSA that are now under study as drug targeting and imaging agents to be used in the treatment and detection of prostate cancer.

The Sean Leng Lab studies the biology of healthy aging. Specific projects focus on chronic inflammation in late-life decline; immunosenescence and its relationship to the basic biological and physiological changes related to aging and frailty in the human immune system; and T-cell repertoire analysis.

The Shawn Lupold Laboratory studies the biology of urologic malignancies, like prostate cancer, to create new experimental diagnostic, prognostic and therapeutic agents.

We study human B cells and neutralizing antibody responses against hepatitis C virus (HCV), hepatitis B virus (HBV), SARS-CoV-2, and respiratory syncytial virus (RSV). Our overarching hypothesis is that understanding the B cell response in individuals who naturally control infections, and those who have been vaccinated, can help us to understand the basic biology behind successful immune responses, leading to design of more effective vaccines. A particular technical strength of our laboratory is high dimensional flow cytometric analysis of antigen-specific B cells, which allows us to phenotype these rare cells, and also to sequence B cell receptor (BCR) repertoires and isolate virus-neutralizing monoclonal antibodies (mAbs).

The Jonathan Zenilman lab conducts research related to sexually transmitted diseases (STDs). We are working to develop biological markers for sexual behavior to use in other research. The lab studies sexual risk behaviors in highly vulnerable populations and studies datasets from the Baltimore City Health Department to understand STD trends and behaviors. Additionally, we study nosocomial infections at Johns Hopkins Bayview Medical Center, with a focus on developing an antimicrobial control program. We also conduct clinical research related to the natural history and microbiology of chronic wounds in the outpatient setting.

The James Hamilton laboratory performs pre-clinical experiments and basic studies investigating liver inflammation, fibrosis, and nuclear receptor signaling. In close collaboration with Dr Svetlana Lutsenko in Physiology, their team performs detailed studies of hepatocyte and non-parenchymal cell isolation, culture, biology and genetic manipulation. Working with models of Wilson disease, a disorder of copper overload, they discovered that hepatic nuclear receptor mediated control of lipid metabolism is a preferential and early target of copper toxicity. Furthermore, targeting nuclear receptors with pharmacologic agonists prevents and reverses liver inflammation and fibrosis.