The Greider lab uses biochemistry to study telomerase and cellular and organismal consequences of telomere dysfunction. Telomeres protect chromosome ends from being recognized as DNA damage and chromosomal rearrangements. Conventional replication leads to telomere shortening, but telomere length is maintained by the enzyme telomerase. Telomerase is required for cells that undergo many rounds of divisions, especially tumor cells and some stem cells. The lab has generated telomerase null mice that are viable and show progressive telomere shortening for up to six generations. In the later generations, when telomeres are short, cells die via apoptosis or senescence. Crosses of these telomerase null mice to other tumor prone mice show that tumor formation can be greatly reduced by short telomeres. The lab also is using the telomerase null mice to explore the essential role of telomerase stem cell viability. Telomerase mutations cause autosomal dominant dyskeratosis congenita. People with this disease die of bone marrow failure, likely due to stem cell loss. The lab has developed a mouse model to study this disease. Future work in the lab will focus on identifying genes that induce DNA damage in response to short telomeres, identifying how telomeres are processed and how telomere elongation is regulated.

The Artemov lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The lab focuses on 1) Use of advanced dynamic contrast enhanced-MRI and activated dual-contrast MRI to perform image-guided combination therapy of triple negative breast cancer and to assess therapeutic response. 2) Development of noninvasive MR markers of cell viability based on a dual-contrast technique that enables simultaneous tracking and monitoring of viability of transplanted stems cells in vivo. 3) Development of Tc-99m and Ga-68 angiogenic SPECT/PET tracers to image expression of VEGF receptors that are involved in tumor angiogenesis and can be important therapeutic targets. 4) Development of the concept of “click therapy” that combines advantages of multi-component targeting, bio-orthogonal conjugation and image guidance and preclinical validation in breast and prostate cancer models.

The research mission of the Zackary Berger Lab is to bridge evidence-based medicine and shared decision-making in the context of patient-centered care. Lab studies investigate how to accomplish this in the common case of uncertainty, while seeking to clarify the ethics of decision-making and empirically describe how shared decision-making is and should be done. Zackary Berger, MD, PhD, is an assistant professor in the Division of General Internal Medicine at the Johns Hopkins School of Medicine. In addition to his work as an internist and primary care physician, Dr. Berger is an associate faculty member in the Berman Institute of Bioethics, and core faculty in the Evidence Based Practice Center as well as the Center for Health Services and Outcomes Research.

The objective of the Xiao Group's research is to study the dynamics of cellular processes as they occur in real time at the single-molecule and single-cell level. The depth and breadth of our research requires an interdisciplinary approach, combining biological, biochemical and biophysical methods to address compelling biological problems quantitatively. We currently are focused on dynamics of the E. coli cell division complex assembly and the molecular mechanism in gene regulation.

The William Bishai Laboratory studies the molecular pathogenesis of tuberculosis. The overall goal of our laboratory is to better understand tuberculosis pathogenesis and then to employ this understanding toward improved drugs, vaccines and diagnostics. Since Mycobacterium tuberculosis senses and adapts to a wide array of conditions during the disease process, it is clear that the regulation of expression of virulence factors plays an important role in pathogenesis. As a result, a theme of our research is to assess mycobacterial genes important in gene regulation. We are also interested in cell division in mycobacteria and the pathogenesis of caseation and cavitation.

The Raman laboratory is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The focus of the laboratory is bench-to-bed side cancer research. We integrate molecular and cellular biology, developmental biology, cancer biology, molecular imaging techniques to study cancer formation and progression. Many of the projects in the lab investigate dysregulated genes in cancer and the translatability of this information to a clinical setting. One such project is to functionally decipher the role of a RNA helicase gene, DDX3, in the biogenesis of multiple cancer types such as breast, lung, brain, sarcoma, colorectal and prostate. Additionally, using a rational drug design approach, a small molecule inhibitor of DDX3 (RK-33) was synthesized and its potential for clinical translation is being investigated.

Research in the Vestibular NeuroEngineering Lab (VNEL) focuses on restoring inner ear function through “bionic” electrical stimulation, inner ear gene therapy, and enhancing the central nervous system’s ability to learn ways to use sensory input from a damaged inner ear. VNEL research involves basic and applied neurophysiology, biomedical engineering, clinical investigation and population-based epidemiologic studies. We employ techniques including single-unit electrophysiologic recording; histologic examination; 3-D video-oculography and magnetic scleral search coil measurements of eye movements; microCT; micro MRI; and finite element analysis. Our research subjects include computer models, circuits, animals and humans. For more information about VNEL, click here. VNEL is currently recruiting subjects for two first-in-human clinical trials: 1) The MVI Multichannel Vestibular Implant Trial involves implantation of a “bionic” inner ear stimulator intended to partially restore sensation of head movement. Without that sensation, the brain’s image- and posture-stabilizing reflexes fail, so affected individuals suffer difficulty with blurry vision, unsteady walking, chronic dizziness, mental fogginess and a high risk of falling. Based on designs developed and tested successfully in animals over the past the past 15 years at VNEL, the system used in this trial is very similar to a cochlear implant (in fact, future versions could include cochlear electrodes for use in patients who also have hearing loss). Instead of a microphone and cochlear electrodes, it uses gyroscopes to sense head movement, and its electrodes are implanted in the vestibular labyrinth. For more information on the MVI trial, click here. 2) The CGF166 Inner Ear Gene Therapy Trial involves inner ear injection of a genetically engineered DNA sequence intended to restore hearing and balance sensation by creating new sensory cells (called “hair cells”). Performed at VNEL with the support of Novartis and through a collaboration with the University of Kansas and Columbia University, this is the world’s first trial of inner ear gene therapy in human subjects. Individuals with severe or profound hearing loss in both ears are invited to participate. For more information on the CGF166 trial, click here.

The Glunde lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The lab is developing mass spectrometry imaging as part of multimodal molecular imaging workflows to image and elucidate hypoxia-driven signaling pathways in breast cancer. They are working to further unravel the molecular basis of the aberrant choline phospholipid metabolism in cancer. The Glunde lab is developing novel optical imaging agents for multi-scale molecular imaging of lysosomes in breast tumors and discovering structural changes in Collagen I matrices and their role in breast cancer and metastasis.

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.