Surinder K. Batra, PhD
Research Summary: What happens when a cell becomes a cancer cell? Can we determine the way this happens, what are the important molecules at the molecular level? Our lab is focused on determining the changes that occur in cancer cell development, especially at the early stages. The goal is to both determine what the important features of cancer development are and to determine what molecules might be important early markers of tumor cells with the goal of early diagnosis.
For more information on Dr. Batra: Website
Steve Caplan, PhD
Research Summary: Cells are constantly interacting with their environments. One form of this interaction that we are studying is the mechanism controlling the uptake of cell-surface receptors and the hormones that they bind. The cell has elaborate mechanisms for this uptake and the process of returning these cell-surface membrane proteins back to the surface of the cell. We are interested in the molecular mechanisms by which this is accomplished and how this process is regulated.
For more information on Dr. Caplan: Website
Kaustubh Datta, PhD
Research Summary: My research interest from my post-doctoral training in Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, to the present time is to study the molecular mechanisms of cancer metastasis. Metastasis is the major cause of cancer-related death. Although several studies to understand the initiation and progression of primary tumors have been performed, metastasis remains an understudied field. It is therefore important to study metastasis in mechanistic detail and to discover novel pathways that have therapeutic implications. I started working independently as an Assistant Professor at Mayo Clinic, Rochester. I moved to the University of Nebraska Medical Center as an Associate Professor and have become a Professor. I also become an active member of Buffet Cancer Research. I am now co-leading the GU Oncology Focus Group of Buffet Cancer Center and work closely with the GU Oncology clinicians. Our research here has been focused on angiogenic growth factors and their role in promoting prostate cancer progression and metastasis. We are particularly working on vascular endothelial growth factor-C (VEGF-C) and its receptor, neuropilin-2 (NRP-2), in prostate cancer and recently observed a novel role of this axis in endocytic trafficking. We observed that enhanced endocytosis in prostate cancer cells due to the activation of the VEGF-C/NRP2 axis promotes cancer-promoting functions such as autophagy and activation of growth factor receptors by facilitating their rapid recycling to the plasma membrane. A comprehensive understanding of this novel function of NRP2 would be therefore crucial to develop an effective therapy against this aggressive, incurable stage of prostate cancer.
For more information on Dr. Datta: Website
Punita Dhawan, PhD
Research Summary: My lab will have an opportunity for students to do a summer rotation studying the mechanisms of regulation of Colon Carcinogenesis and validate the therapeutic potential of novel protein/s. My lab is focused on understanding the molecular processes of neoplastic growth and progression, to help improve clinical management. We are investigating how the interface between mammalian cells and the outside environment is modulated during disease processes, and its causal significance with special emphasis on tight junction proteins. My lab is largely focused on developing new therapeutic molecules in the regulation of colonic homeostasis and tumorigenesis. We have recently shown a novel and currently unexplored role of Claudin-1 in the regulation of MMP-9/Notch expression, to regulate epithelial homeostasis and also developing a small molecule inhibitor and determine its therapeutic potential. In addition, we are understanding the non-tight junctional role of claudin-7 in cell-matrix and cell-cell interaction. To study we use mouse models, in vitro mouse organoid/tumoroid cultures, and cell culture models.
For more information on Dr. Dhawan: Website
Maneesh Jain, PhD
Development of diagnostics and therapeutics against cancer and allied diseases.
My interest has been to develop antibody-based strategies for targeted therapy and diagnosis of diseases, particularly cancer. Our research involves the development of genetically engineered antibody fragments for improved radioimmunotherapy of solid tumors. We are trying to optimize radioimmunotherapy of solid tumors by modifying the molecular design of antibody fragments and introducing sequences that will enhance the uptake and/or retention of radiolabeled antibodies in the tumor tissues without altering their distribution in non-target tissues. Recently, we demonstrated the utility of cell-penetrating peptides in improving the tumor retention antibody fragments.
The other area of our research involves the development of serum assays for the early diagnosis of lethal pancreatic cancer. We are trying several approaches to develop sensitive mucin-based serum assays utilizing the antibodies that we have generated. In collaboration with several groups, we are trying to develop a multimarker nanoparticle-based assay for the early diagnosis of pancreatic cancer. We are also trying to use the antibodies for disrupting the signaling pathways mediated by their targets for therapeutic intervention and engineering the antibodies for human use. Additionally, we are trying to use the antibodies and antibody fragments for the delivery of nanoparticle-encapsulated drugs to various cancers. The following projects are currently in progress:
- Early diagnosis of pancreatic cancer. The project involves the development of mucin-based serum assays(s) for the early detection of pancreatic cancer using various approaches.
- Therapy against prostate and other cancer using radiolabeled antibody constructs. We are interested in developing a multi-antigen (EGFRvIII, MUC4, and TAG72) targeted radioimmunotherapy using a cocktail of antibody fragments.
- Studying the involvement of altered signaling pathways in cancer and exploiting the information cancer therapy. We are trying to understand the role(s) of RUNX family transcription factors in the pathogenesis of pancreatic cancer. Specific focus is on the identification of the target gene(s) regulated by RUNX3 and their involvement in the development and progression of pancreatic cancer.
- Studying the involvement of altered EGFR signaling in the development of pancreatic cancer. We are studying the role of mutant EGFR receptors, particularly EGFRvIII, in pancreatic cancer pathogenesis. These studies will form the basis of developing new therapeutic strategies using anti-EGFRvIII-specific antibodies for targeting pancreatic cancer.
For more information on Dr. Jain: Website
Sukhwinder Kaur, PhD
Research Summary: Lethality of disease is dictated by its stage at the time of diagnosis. The development of a combinatorial signature along with ultrasensitive technologies for marker detection is key to improved diagnosis and prognosis. My studies focus on developing a combined diagnostic and prognostic panel, utilizing disease associated altered gene, protein, metabolic, and exosomal signatures. We are using machine learning based AI approaches for biomarker discovery that provides high accuracy to diagnose the early stages of the disease. While working on biomarkers, we observed specific elevation of the megadalton glycoprotein MUC5AC and MUC5B in early stage disease. Further, the elevation of these mucins was stage and metastasis-specific, throughout PC progression. Using a comprehensive serum set (N=922), we demonstrated that MUC5AC is present at high levels in the blood of pancreatic cancer patients and has high potential as a diagnostic and prognostic biomarker in combination with CA19.9. Further, we identified a combination of MUC4, MUC5AC, and CA19.9 for early diagnosis of pancreatic cancer. Next, we are focusing on developing sensitive technologies (Surface Enhanced Raman Spectroscopy) to detect this multi-marker panel. The other focus of my research involves delineating molecular mechanisms of oncogenic signaling by differentially expressed biomarkers in the progression and metastasis of various malignancies. We are focusing on delineating the functional significance of MUCs and HOX genes on tumor progression, metastasis, and chemoresistance. Currently, studies focus on:
- Development of imaging biomarkers for early disease detection
- Machine learning based biomarker identification and validation
- Identification of exosomal surface, protein, and miRNA signature for diagnosis and prognosis of pancreatic cancer.
- Meta-analyses of biomarkers for Colonic polyp stratification
- Delineating the role of differentially expressed oncogenes in pancreatic cancer progression and metastasis.
For more information on Dr. Kaur: Website
Ming-Fong Lin, PhD
Research Summary: Why do cancer cells grow uncontrollably? We are trying to answer this question in prostate cancer. Our approach is to study the regulation of protein phosphorylation, the addition of a phosphate group to proteins. This is known to control the activity of many cellular proteins important for cell growth. We are concentrating on prostatic acid phosphatase (PCAP), which can remove phosphate groups from proteins, with the goal of trying to determine if PCAP is important for prostate cancer development.
For more information on Dr. Lin: Website
Rebecca Oberley-Deegan, PhD
Research Summary: The Oberley-Deegan laboratory is focused on understanding the role that free radicals play in normal tissue toxicity during cancer therapy. Specifically, we are focused on mitigating fibrosis and hematological toxicities associated with radiation and chemotherapy used for cancer treatment. We are also interested in the role that free radicals play in cancer progression.
For more information on Dr. Deegan: Website
Moorthy P. Ponnusamy, PhD
Research Summary: Ovarian cancer is a highly lethal disease that represents a great clinical challenge in gynecologic oncology. It is asymptomatic until the disease is in the late stage, causing it to have the highest fatality-to-case ratio of all gynecologic malignancies. It is essential to analyze the diagnostic and prognostic markers for ovarian cancer to manage this lethal disease. My first goal is to analyze the role and mechanism of membrane-bound mucins (MUC4 and MUC16) in the progression of ovarian cancer. We have recently shown that MUC4 plays a major role in ovarian cancer cell motility and metastasis, in part, by altering actin arrangement and potentiating HER2 downstream signaling in these cells. In addition, we have identified that MUC4 plays a role in inducing epithelial-mesenchymal transition (EMT) in ovarian cancer cells. This occurs through upregulation of N-cadherin expression that leads to the enhanced metastatic potential of human ovarian cancer cells.
Further, based on our observations that MUC4 interacts with and stabilizes the receptor tyrosine kinase ErbB2 (HER2), we have hypothesized that the interaction between MUC4 and HER2 could be at least partly responsible for the resistance of HER2 expressing breast cancers to Trastuzumab (Herceptin). This project is to investigate the role of MUC4 in the resistance of breast cancer cells to Trastuzumab and identify the underlying mechanism. This project explores an innovative approach to tackle Trastuzumab resistance by targeting MUC4 in combination with ErbB2, which should provide a synergistic outcome by unmasking the epitope (masked by MUC4) and thus potentially improve the outcome for breast cancer patients.
We have recently demonstrated that MUC4 overexpression leads to an enriched ovarian cancer stem cell population either directly or indirectly through HER2. Further, we are investigating the biological consequence and drug resistance property of MUC4-mediated stabilization of HER2 in ovarian cancer stem cells and its effect on the pathogenesis of ovarian cancer. In the future, this study would be helpful for MUC4-directed therapy for the ovarian cancer stem cell population.
Role and Mechanism of hPaf1/PD2 in Cancer Stem Cells: My second goal is to identify and characterize the cancer stem cell populations in different cancers. Over the last several years, it has been identified that a small population (less than 5%) of cancer cells, referred to as “Cancer Stem Cells (CSCs)” or “side population cells (SP)”, is responsible for the aggressiveness, metastasis, and resistance of ovarian cancer cells to therapy. Based on our previous study on the role of human polymerase association factor 1/pancreatic differentiation 2 (hPaf1/PD2) in the maintenance of self-renewal in mouse embryonic stem cells, I hypothesize that hPaf1/PD2 may play a role in regulating self-renewal of CSCs. This project seeks to investigate the role and mechanism of a novel molecule hPaf1/PD2 in cancer stem cells. The identification of cancer stem cell-specific marker hPaf1/PD2 and its role in CSC maintenance would provide extremely important information that is critical in advancing towards the long-term goal of developing novel therapeutic strategies for the cancer stem cell population.
For more information on Dr. Rachagan: Website
Satyanarayana Rachagan, PhD
Research Summary: My lab research mainly focuses on the following areas:
- Identification of miRNA signature for diagnosis and prognosis of pancreatic cancer
- Study role of mucins in pancreatic and colorectal cancer pathogenesis using cell and Genetically engineered mouse models.
- Chemoprevention and novel combination therapies for pancreatic and colorectal cancer.
- Diet mediated alterations of the microbiome in inflammatory bowel disease
- Cancer metabolism in pancreatic cancer
For more information on Dr. Rachagan: Website
Amar Singh, PhD
Research Summary: Our research focuses upon understanding the molecular undertakings of Inflammatory Bowel Disease, colorectal and renal cancer with specific emphasis on the regulation of the neoplastic transformation of the epithelial cells and the cross-talk between epithelial and immune homeostasis. We have generated novel genetically engineered mouse lines, innovative mouse models of IBD and colitis-associated cancer, and established in vitro organ culture in the pursuit of our studies. In addition, we are developing patient-derived organoids and tumor xenografts from known disease stages and variable therapeutic response and ability of longitudinal analysis of the IBD-associated carcinogenesis in genetic or chemical-induced colon cancer using the Carl-Storz mouse endoscope.
For more information on Dr. Singh: Website
Paul L. Sorgen, PhD
Research Summary: Cells next to each other in a tissue form strong intercellular connections. One form of these connections is gap junctions, which form pores that can allow the passage of small molecules from one cell to its neighbor. We are studying one of the molecules that are important for the formation of gap junctions, the connexins. Our goal is to understand the molecular structure of the connexins and how they regulate gap junction formation and intercellular communication.
For more information on Dr. Sorgen: Website
Justin Mott, MD, PhD
Research Summary: Injury and inflammation of the liver are important parts of non-alcoholic fatty liver disease. A project in the Mott Lab is currently studying how fatty acids cause injury and inflammation in cells lining the bile ducts. This project involves measuring the response of cultured cells to fatty acids. Open questions that are being studied include determining the nature of the initial toxic signaling by fatty acids and identifying protective strategies to reduce injury. Separately, they are investigating cell death pathways in cholangiocarcinoma, an aggressive liver cancer
For more information on Dr. Mott: Website
Melissa Teoh-Fitzgerald, PhD
Research Summary: For years scientists have studied breast cancer cells to varying degrees to determine why and how they form, thrive and communicate with one another and in some cases resist treatment. Towards this goal, my group is interested in understanding the stroma cells surrounding the cancer cells in the tumor, such as cancer-associated fibroblasts and cancer-associated macrophages that support the cancer cell. My research will address the following questions: Why are the stroma cells so important? What role do they play in helping the tumor to survive, thrive, and become more aggressive? And how can these stroma cells be altered to stop the progression of cancer? My lab will look at breast cancer-associated fibroblasts that produce proteins and factors that support the cancer cells in hopes of learning more about them. Specifically, we will investigate how oxidative stress influences the communication between the cancer cells and their surrounding fibroblasts. By looking into the microenvironment of breast tumors, we hope this leads to targeted therapies that attack not only the cancer cells but also block the supportive role of fibroblasts.
For more information on Melissa Teoh-Fitzgerald: Website
Ricia “Kate” Hyde, PhD
Research Summary: In the Hyde lab, we study a subtype of acute myeloid leukemia that is caused by an inversion of chromosome 16. This inversion generates a fusion gene between the transcription factor CBFB and the gene for Smooth Muscle Myosin Heavy Chain, MYH11. The fusion gene is called CBFB-MYH11 and encodes the protein CBFβ-SMMHC. Expression of the fusion protein is the initiating event in leukemogenesis, but its mechanism is not well understood. Using genetic mouse models, tissue culture, and molecular biology techniques, we are studying the gene expression changes induced by CBFβ-SMMHC and the co-factors required for its activity. We are also studying the leukemia stem cell population induced by CBFβ-SMMHC and the factors required for their survival. The long term goal of our laboratory is to identify potential drug targets for the development of new therapies for patients with acute myeloid leukemia.
For more information on Ricia Hyde: Website