Xuefeng Liu, MD, Associate Professor
Director of Telomeres & Cell Immortalization Program
Dr. Liu is an Associate Professor in the Department of Pathology, serves as Director of Telomeres and Cell Immortalization Program within Center for Cell Reprogramming (CCR) and Scientific Director of Conditional Reprogramming Laboratory (CRL). Dr. Liu’s research interests focus on the roles of papillomavirus oncoproteins and telomerase in cell immortalization which is a very early stage of human cancer. The E6 and E7 proteins from high risk HPVs were first identified as targeting to disruption of cell cycle controls. The simultaneous expression of E6 and E7 appears to be requisite for cervical cancer. E6 protein has the unique property of increasing cellular telomerase activity by engaging both transcriptional and post-transcriptional mechanisms and this activation has been considered a critical and rate-limiting step in the progression to malignancy. His work has defined two major cellular targets for E6 oncoprotein, Myc and hTERT, which play a critical role in cell immortalization (PNAS 2003, JBC 2005, JVI 2007 and 2008, Virology 2008, BCTR 2009). Recently, his group has discovered that the E6 protein also interacts directly with the hTERT protein (PNAS 2009) and that E6 and E7 induce immortalization through non-telomere/non-catalytic functions of hTERT (PLoS Pathogens 2013). These studies are funded by a new grant from NIH. Together with Dr. Richard Schlegel, Dr. Liu recently co-invented a new cell technology, CRC technology, which was described in the Journal of Clinical Investigation (2010), American Journal of Pathology (2012, 2013), New England Journal of Medicine (2012), PNAS (2012), PLoS ONE (2014) and Oncotarget (2014). This technology allows us to rapidly propagate patient-derived normal and tumor (diseased) cells infinitely. Importantly, he utilized this technology to identify infection of HPV 11 and an effective therapy for a patient with metastatic pulmonary tumors arising from laryngeal papillomatosis. These results represent the first successful example of individualized therapy (NEJM). Dr. Liu has trained more 50 researchers from NIH/universities - Harvard, Yale, Duke, Stanford, Arizona, Wake Forest, UNC, Thomas Jefferson, CUHK, Mayo, MD Anderson to name a few - as well as scientists at Georgetown University to use CRC technique in their research. This training also resulted in a broad spectrum of intramural and extramural collaborations. Currently, Dr. Liu is leading the program of Cell Immortalization and direct (Scientific) Conditionally Reprogramming Laboratory (CRL) together with Dr. Ewa Krawczyk. He is also collaborating on different aspects/applications of CRC with many extramural (NIH, Harvard, MGH, MD Anderson, UNC, Mayo, etc.) and intramural (laboratories of Drs. Priscilla Furth, Anna Reigel, Anton Wellstein, Yun-Ling Zheng, Maria Laura Avantaggiati, Tony Dritchilo, Chip Albanese, etc.). As principle investigator or co-investigator, his research is currently supported by several grants from NIH (R01, R33, R21), Cheery Blossom Breast Foundation, MedStar Health Research Institute and NCI-CCSG. His ongoing projects include the role of non-canonical functions of hTERT in cell immortalization, role of HPV, mutant p53 and Myc in Head and Neck Tumor and cervical cancer, role of p53 and cytoskeleton remodeling in conditionally reprogramming, in vitro and in vivo differentiation of CRCs. He currently serves as an Academic Editor of PLoS ONE and as a board member of Virus Genes, and as a reviewer for PNAS, Cancer Research, Nucleic Acid Research, Journal of Virology, International Journal of Cancer, International Journal of Biochemistry and Cell Biology, Journal of Cellular and Molecular Medicine, Carcinogenesis, PLoS One, Molecular Cancer Research and Gynecologic Oncology. Dr. Liu obtained his medical and biochemistry training in China and postdoctoral training with Dr. Raymond Schinazi at Emory University and Dr. Thomas Zheng at National Cancer Institute (NCI), respectively.
Abdul Matin Mondal, PhD, Research Instructor
Dr. Mondal started serving as a Research Instructor at the CCR in November 2014. Dr. Mondal’s current ongoing projects include studying the following: 1) profile and roles of p53 and its splicing variants in CRC; 2) modifications of p53 proteins during conditional reprogramming—a collaboration with Dr. Ettore Appella's group at the NCI; and, 3) hair follicle formation of skin CRCs in mice—a collaboration with Dr. Rajesh Thangapazham and Dr. Thomas Darling at UHUHS. Dr. Mondal received his BTech in Pharmaceutical Technology and MTech in Biotechnology from the Jadavpur University, Kolkata, India. Subsequently, he earned his doctoral degree from the All India Institute of Medical Sciences, New Delhi, India. Before joining CCR, he obtained his postdoctoral training under Dr. Curtis C. Harris at the National Cancer Institute, where he focused his research on understanding the molecular mechanisms of cellular senescence, aging and cancer. He made a significant contribution to the discovery of the endogenous regulation of cellular senescence by natural p53 isoforms, D133p53 and p53β (Nature Cell Biology, 2009). He also played a key role in a study demonstrating the feedback regulation between p53 and the telomere-binding protein complex (Nature Cell Biology, 2010). Dr. Mondal has also had established that p53 isoforms, D133p53 and p53β are physiological regulators of aging- and tumor-associated replicative cellular senescence of human CD8+ T lymphocytes in vivo (Journal of Clinical Investigation, 2013).
Lama Alhawas, PHD candidate, Graduate Student
Lama is a first year PhD student at the Biochemistry Department and currently serves as a Research Intern for Dr. Liu. She joined CCR in January 2015 and is working on her thesis project with Dr. Liu and the immortalization team. She is currently focusing on multiple projects, including mechanisms of cell immortalization and conditional reprogramming and tumor heterogeneity using 2D and 3D cultures as well as animal experiments. She earned her BS degree in Biochemistry, with a minor in Psychology, from the University of Ottawa. She then joined Georgetown University in the department of Biochemistry and Molecular Biology and received her MS degree in 2014.
Dr. Hang Yuan, PhD, Associate Professor
Director of HPV Biology Program
Dr. Yuan received his PhD from Wake Forest School of Medicine. He started his postdoctoral training at Georgetown University Medical Center in 1998. Currently, he is an Associate Professor in the Department of Pathology. Dr. Yuan moved to Georgetown after the first-generation HPV vaccine was developed in Dr. Schlegel’s lab and became the group leader on vaccine development. His work, in collaboration with Bob Garcea at the University of Colorado, led to the second-generation cervical cancer vaccine, which can potentially cut production cost by 90%. This method led to a patent and it is hopeful that this second generation vaccine will be utilized in developing countries, where deaths from cervical cancer are most prevalent. This same technology was the basis of third generation vaccine studies which was funded by Gate's Foundation (Grand Challenges in Global Health 2004-2009) and NIH (RAPID 2001-2003) and intended to combine a prophylactic with a therapeutic vaccine. In the course of his animal model studies, Dr. Yuan discovered and characterized Canine Papillomavirus type 2. This study and his subsequent work established himself as the leading expert in canine papillomavirus field. This canine model study has received an NIH R01 award. Dr. Yuan has also made significant contributions toward conditional reprogramming of epithelial cells research. He contributed to the finding that feeder cells are required for immortalization and he established 3D cultures for the CRC cells, thereby allowing the analysis of the differentiation potential of these cells. He has also demonstrated the tumorigenicity of the CRC tumor cells successfully in animals. More importantly, he successfully utilized conditionally reprogrammed cells to identify viral mutations in a rare case of HPV-induced lung tumors and used this to identify an effective therapy. The advance was seen as an exciting demonstration of the use of conditional reprogramming in personalized cancer medicine. His seminar presentation was awarded Geo von Krogh Prize by the Papillomavirus Society in the 27th International Papillomavirus Conference and Clinical Workshop (2011). The results were published on The New England Journal of Medicine in 2012, where Dr. Yuan was the first author.
Dan Zhou, MS, Research Assistant
Dan is currently serving as a Research Assistant under Dr. Yuan’s direction. She is managing the papillomavirus vaccine development and production. Additionally, she is using a three dimensional Air-liquid Interface (ALI) culture to analyze HPV-related cancers in vitro. She has assisted Dr. Yuan with various important projects on Human and Canine Papillomavirus since 2006. She has contributed significantly in the discovery of novel papillomaviruses. Dan earned her MS in Agronomy from Hunan Agriculture University, China.
Faris Alkhilaiwi, PhD Candidate, Graduate Student
Faris’ research is focused on understanding the cross-talk between healthy cells and tumor cells in HPV-related cancer and what makes the healthy cells turn into tumors cells. Faris earned his BS in clinical pharmacy from King Abdulaziz University and a Masters in Biotechnology from Georgetown University. He is a PharmD candidate in Biochemistry, Molecular, and Cellular Biology at Georgetown University. After graduating he joined the PhD program.
Frank A. Suprynowicz, PhD, Assistant Professor
Dr. Suprynowicz has been an Assistant Professor in the Department of Pathology since 1997. He is a graduate of the University of California – Berkeley’s Department of Zoology, Cell Biology and took his Postdoctoral Fellowship at Johns Hopkins University Medical School’s Department of Cell Biology and Anatomy. His research also took him to the Research Institute of Scripps Clinic in California where he worked with the Cell Biology Group. He continued to the National Institutes of Health as a Senior Staff Fellow working in Biochemistry, Cell Physiology, and Cell Biology. His research interests include: The application of quantitative biochemical and cell biological methods to understand intracellular signaling pathways essential to cellular reprogramming and to identify extracellular factors that induce reprogramming. The bilateral approach towards understanding the basic biology of CRCs is intended to develop an improved technology that utilizes a minimal, completely defined set of conditions to reprogram primary cells. Most recently, he led the research which established that the CRC technique rapidly and reversibly reprograms primary epithelial cells to an adult stem cell-like state that maintains tissue-specific developmental potential.
Dan Hartmann, PhD, Adjunct Professor
Dr. Hartmann serves as an Adjunct Professor in the Department of Pathology. Dr. Hartmann is working in collaboration with Dr. Frank Suprinowicz, using antibody-based proteomic arrays and other biochemical techniques. Dr. Hartmann is also involved in the study of HPV-associated chromosomal translocations in malignant tumors, using the FISH (fluorescent in situ hybridization) technology. Prior to joining CCR, he served for many years as a Professor of Pathology and the Director of the Molecular Diagnostic Laboratory at Georgetown University Hospital from which he retired in 2011. He is the author of over sixty publications and brings with him his experience in molecular pathology. For the past year, he has been involved in a team effort to identify the components required for the “Conditionally Reprogrammed Cell” (CRC) method. In addition, he has been the Director for a Post-Graduate Biotechnology course for the past ten years entitled, “Biotechnology-Based Human Diagnostics” in the Department of Biochemistry and Molecular & Cellular Biology. He is the author/co-author of three U.S. patents, including one where artemisinin - a plant-derived anti-malarial drug--is currently in clinical trial for patients with cervical dysplasia and cancer.
Seema Agarwal, PhD, PhD, Associate Professor
Dr. Agarwal is an Associate Professor for the Department of Pathology. In her current position, she focuses on salivary gland tumors, melanoma, gilioblastoma, lung and breast cancers. Her research group has planned to develop an in vitro cell line model system that will include cell types from stromal component and tumor epithelial cells using modification of CRC technology. She comes to the center with extensive experience in organic synthesis, biochemistry, genetics, genomics, molecular and cellular biology in order to gain the comprehensive understanding of complex diseases like cancer. One of her research interests is in identifying different signaling pathways that contribute in cancer growth and metastasis and to develop drug combination therapies. Another field of interest is to quantitatively measure proteins and microRNAs in clinical samples to develop novel biomarkers for identifying patients that will be at high risk of developing metastasis as well as biomarkers that will be useful in identifying patients that will be either resistant or sensitive to a given treatment regimen. Her current research focus is in developing suitable cell model systems (2D and 3D) that can better predict treatment to therapy. Her group recently have been using two methods to culture primary tumors with an ultimate goal of recapitulating primary human cancers to better understand the biology of cancer initiation, progression and metastasis; identify novel drug targets; de novo and acquired resistance to drugs, to utilize these systems to identify novel drug combination for personalized medicine concept/approach. First method involves growth of cancer cells in 3D directly from biopsy or FNA samples from breast cancer patients that are enriched in stem cell like properties. Second method is to grow, expand and maintain primary cell cultures derived directly from patient's tissue samples (biopsies and FNAs) using feeder cells and ROCK inhibitor. She is a graduate of Allahabad University (India) and Lehigh University (USA), where she earned her PhDs in Organic Chemistry and Biochemistry, respectively. She did her postdoctoral work at Yale University with Drs. Shirleen Roeder and Michael Snyder. Before joining Georgetown University, she was a research faculty at Yale University where she was associated with Dr. David Rimm’s research group.
SUJATA CHOUDHURY, PHD, RESEARCH ASSOCIATE
Dr. Choudhury is currently a Research Specialist in “Immortalization Team” led by Dr. Liu. Her ongoing projects include: (1) feeder free CRC system; (2) role of p53 in normal and tumor CRCs; (3) Role of Rock1 and Rock 2 in cell reprogramming; and, (4) role of mutant p53 and their turnover in cancer progression. Previously, Dr. Choudhury worked on DNA damage and repair for a long period of time and then she worked with Dr. Maria Laura Avantaggiati on role of mutant p53 in cancer progression. She was the first author on the paper describing newly degradation pathway as well as the possible role played by autophagy during tumor evolution driven by mutant p53. She obtained her Ph.D.in Cell Biology and Biochemistry in India.
Chen Chen, MS, Research Assistant
Chen began working as a Research Assistant with Dr. Seema Agarwal’s group in May, 2014. He is currently working on various projects including, use of modified CRC culture conditions to establish and maintain the culture of brain and salivary tumor cells as well as establishing 3D cultures. In addition, Chen is also involved in resolving the tumor-normal mixed tumor CRC cultures. He will also be involved in characterizing these established cultures using various cellular and molecular biology techniques. Previously, Chen has served as a Research Assistant in the CRC Lab for a year and a half. He was responsible for processing tissues from the MedStar Georgetown University Hospital and used the CRC method to culture epithelial cells. During his short time in the CRC Lab, Chen established over 200 CRC lines from various tissue types.
Ewa Krawczyk, PhD, Research Instructor
CRC Lab Manager
Dr.Krawczyk joined Department of Pathology as a postdoctoral fellow in 2005. She spent her postdoctoral training on studies of properties of E5 – one of HPV proteins, and its interactions with the host cell proteins. She determined one of the most fundamental properties of E5 protein, that is, its orientation in cellular membranes of infected cells. She discovered the basis of koilocytosis, a particular transformation of HPV-infected cells that has been known and used as a diagnostic hallmark of HPV infection for decades, but without knowledge of underlying processes. Her further work has shown how E5 interacts with certain cellular proteins, including those involved in vesicle trafficking, and alters the distribution of these proteins within the cell. Dr. Krawczyk was promoted to Research Instructor in 2011. She was also designated as the CRC Lab Manager to establish and lead a new project: a laboratory for Conditionally Reprogrammed Cells (CRC) cultures. She has already collected a substantial number of samples and determined optimal culture techniques as well as collaborating with many investigators both within and outside of Georgetown University. Dr. Krawczyk is a graduate of Warsaw University and Warsaw Medical University, both in Warsaw, Poland, where she earned her MS and PhD in Animal Embryology and Medical Microbiology, respectively.
Jie Lu, MS, Research Assistant
Jie serves as a Research Assistant under the supervision of Dr. Ewa Krawczyk in the CRC Lab. He is responsible for processing tissues and using the conditional reprogramming method to establish new cell lines. Jie has one year of previous work experience in cell biology prior to joining the CRC Lab. He earned his MS in Biochemistry and BS in Biotechnology at Georgetown University and Beijing Forestry University, respectively.
Haewon Park, MPH, CRA, Director of Business Operations
Haewon serves as the Director of Business Operations for the CCR and the Department of Pathology. She is responsible for financial and administrative leadership in management of all business functions for the center, including business outreach initiatives, negotiating commercial and research projects and promoting the growth and awareness of the CRC technology. She comes to the center with extensive experience in pre- and post-award management, financial management, budget development and grants and contracts administration from working with Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS) and Department of Family Medicine Clinical Research Division at Georgetown University Medical Center. She is a graduate of James Madison University and George Washington University, where she earned her BS and MPH, respectively. Additionally, she is a Certified Research Administrator (CRA).
Vera Simic, BS, Lab Manager
Vera works as the Lab Manager/Program Coordinator for the CCR. She earned her BS in Molecular Biology and Physiology from University of Belgrade, Faculty of Biology, Serbia, Yugoslavia and has been working in Dr. Schlegel’s laboratory since March, 2002. Vera is responsible for laboratory management and finances as well as maintaining and conditionally reprogramming tissue culture cells. Vera assists various research groups with their projects, which resulted in co-authorship in several publications.
Amy Botello, MA, BA, Administrative Assistant
Amy serves as the Administrative Assistant for the CCR. She is responsible for the daily office operations for Dr. Schlegel. Amy has been with Administration at Lombardi Comprehensive Cancer Center for over two years, working with both the departments of Oncology and Pathology. She earned a Bachelor of Arts degree as well as a Masters of Arts Degree at Oral Roberts University and Regent University, respectively.