The Fukunaga Lab uses multidisciplinary approaches to understand the cell biology, biogenesis and function of RNA-binding proteins and small silencing RNAs from the atomic to the organismal level. The lab studies (1) biology and molecular functions and mechanisms of uncharacterized RNA-binding proteins, and (2) how small silencing RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), are produced and function. Mutations in the RNA-binding protein and small RNA genes cause many diseases, including cancers. We use a combination of biochemistry, Drosophila genetics, molecular biology, cell culture, and next-generation sequencing, to answer fundamental biological questions and also potentially lead to therapeutic applications to human diseases.

Epstein-Barr virus and Kaposi's sarcoma herpesvirus are found in association with a variety of cancers. Our laboratory studies are aimed at better defining the role(s) of the virus in the pathogenesis of these diseases and the development of strategies to prevent, diagnose or treat them. We have become particularly interested in the unfolded protein response in activation of latent viral infection. Among the notions that we are exploring is the possibility that activation of virus-encoded enzymes will allow the targeted delivery of radation. In addition, we are investigating a variety of virus-related biomarkers including viral DNA, antibody responses, and cytokine measurements that may be clinically relevant.

At the Suman Paul laboratory, we are focused on developing new antibodies and cell therapies for cancer treatment. Our team of researchers are dedicated to identifying novel targets, mechanisms for cancer therapy and developing innovative solutions to improve patient outcomes. We work closely with basic science researchers and clinicians to accelerate the translation of our discoveries into clinical practice.

Research in the Antony Rosen Lab investigates the mechanisms shared by the autoimmune rheumatic diseases such as lupus, myositis, rheumatoid arthritis, scleroderma and SjogrenÕs syndrome. We focus on the fate of autoantigens in target cells during various circumstances, such as viral infection, relevant immune effector pathways and exposure to ultraviolet radiation. Our recent research has sought to define the traits of autoantibodies that enable them to induce cellular or molecular dysfunction. We also work to better understand the mechanisms that form the striking connections between autoimmunity and cancer.

Our research is focused on understanding the basic mechanisms of programmed cell death in disease pathogenesis. Billions of cells die per day in the human body. Like cell division and differentiation, cell death is also critical for normal development and maintenance of healthy tissues. Apoptosis and other forms of cell death are required for trimming excess, expired and damaged cells. Therefore, many genetically programmed cell suicide pathways have evolved to promote long-term survival of species from yeast to humans. Defective cell death programs cause disease states. Insufficient cell death underlies human cancer and autoimmune disease, while excessive cell death underlies human neurological disorders and aging. Of particular interest to our group are the mechanisms by which Bcl-2 family proteins and other factors regulate programmed cell death, particularly in the nervous system, in cancer and in virus infections. Interestingly, cell death regulators also regulate many other cellular processes prior to a death stimulus, including neuronal activity, mitochondrial dynamics and energetics. We study these unknown mechanisms. We have reported that many insults can trigger cells to activate a cellular death pathway (Nature, 361:739-742, 1993), that several viruses encode proteins to block attempted cell suicide (Proc. Natl. Acad. Sci. 94: 690-694, 1997), that cellular anti-death genes can alter the pathogenesis of virus infections (Nature Med. 5:832-835, 1999) and of genetic diseases (PNAS. 97:13312-7, 2000) reflective of many human disorders. We have shown that anti-apoptotic Bcl-2 family proteins can be converted into killer molecules (Science 278:1966-8, 1997), that Bcl-2 family proteins interact with regulators of caspases and regulators of cell cycle check point activation (Molecular Cell 6:31-40, 2000). In addition, Bcl-2 family proteins have normal physiological roles in regulating mitochondrial fission/fusion and mitochondrial energetics to facilitate neuronal activity in healthy brains.

The Janet Staab Lab performs basic and translational studies to understand bacterial and fungal/host interactions utilizing human intestinal organoids and colon cancer cell lines.

Dr. Christine Durand, assistant professor of medicine and oncology and member of the Johns Hopkins Kimmel Cancer Center, is involved in clinical and translational research focused on individuals infected with HIV and hepatitis C virus who require cancer and transplant therapies. Her current research efforts include looking at outcomes of hepatitis C treatment after solid organ transplant, the potential use of organs from HIV-infected donors for HIV-infected solid organ transplant candidates, and HIV cure strategies including bone marrow transplantation. Dr. Durand is supported by multiple grants: • R01 from the National Institute of Allergy and Infectious Diseases (NIAID) to study HIV-to-HIV organ transplantation in the US. • K23 from the National Cancer Institute (NCI) to study antiretroviral therapy during bone marrow transplant in HIV-1 infection. • U01 from the NIAID to study HIV-to-HIV deceased donor kidney transplantation. U01 from the NIAID to study HIV-to-HIV deceased donor liver transplantation.

The Constance Monitto Lab conducts clinical research on pediatric pain management as well as basic science studies on chemotherapy resistance. In our pediatric pain management research, we work to assess the impact of low-dose opioid antagonism on opioid-related side effects, such as nausea and vomiting. We also analyze data on current methods of pediatric pain management in the United States. In addition, our team uses basic science studies to assess the success of epigenetic gene regulation on the development of resistance to chemotherapeutic agents in cancer.

Utilizing a combination of tissue-based, cell-based, and molecular approaches, our research goals focus on abnormal telomere biology as it relates to cancer initiation and tumor progression, with a particular interest in the Alternative Lengthening of Telomeres (ALT) phenotype. In addition, our laboratories focus on cancer biomarker discovery and validation with the ultimate aim to utilize these novel tissue-based biomarkers to improve individualized prevention, detection, and treatment strategies.

The Foda lab conducts basic, translational, and clinical research on the early detection, prevention, and interception of gastrointestinal cancers. In collaboration with the other member of the Johns Hopkins Cancer Genomics Lab (https://cancergenomicslab.com/), the group develops and applies whole-genome sequencing-based liquid biopsy methods for the early detection and monitoring of gastrointestinal cancers. These approaches are tested and validated in large multi-national cohorts through international collaborations. Dr. Foda directs the Johns Hopkins Hereditary Colorectal Cancer Registry, which facilitates clinical research related to Familial Adenomatous Polyposis, Lynch syndrome, and other hereditary polyposis conditions.