Faculty
Junjie Chen, Ph.D. (Chairman)
The overall goal of the Chen laboratory is to understand the molecular mechanisms underlying genomic instability and tumorigenesis. The maintenance of genomic integrity following DNA damage depends on the coordination of DNA repair with cell cycle checkpoint controls. The integrity of the DNA damage response pathway is crucial for the prevention of neoplastic transformation, as suggested by the fact that many proteins involved in these pathways are tumor suppressors including p53, ATM, Chk2, BRCA1 and BRCA2. His group has discovered and studied many new components involved in DNA damage pathways. Recently, Dr. Chen’s group also ventured into other areas of genomic instability, including mitotic regulation, cellular senescence and aging. He demonstrated a mitotic checkpoint protein Chfr is a tumor suppressor, which controls proper mitotic progression via its regulation of several key mitotic kinases. His lab is also studying a protein deacetylase SIRT1 and its role in aging and tumorigenesis.
Boyi Gan, Ph.D.
Dr. Gan's lab studies metabolic signaling in cancer development, aging and stem cell maintenance, with the long-term goal of applying the acquired knowledge toward the development of specific and effective rational therapies targeting metabolic pathways in cancer treatment. One project focuses on the role of FoxO/TSC/LKB1 tumor suppressor network in cancer metabolism, aging and stem cell biology. In another project, they are studying the genetic and metabolic network in kidney cancer, one of the major metabolic cancer types. One of the major approaches utilized in our studies is the sophisticated genetically engineered mouse models.
Zihua Gong, Ph.D.
Dr. Gong's research includes: 1) the identification of new protein complexes involved in DNA damage response using a proteomic approach. This work will expand our understanding of the complexity of the signal transduction network in DNA damage pathways. 2. Increased understanding of the DNA damage protein TopBP1 in the replication checkpoint pathway. We will work to define the signaling pathway that controls the recruitment and function of TopBP1 following replication stress. 3. Study the role of tyrosine kinases in the cancer development. We hope to reveal new tyrosine kinases complex for developing or inhibiting cancer.
Jingsong Yuan, Ph.D.
Dr. Yuan’s main interest is in the underlying molecular mechanisms that result in genomic instability and tumorigenesis, specifically, MRN (MRE11-RAD50-NBS1) complex which has been implicated in the detection of DNA double-strand breaks (DSBs), DNA ends resection, recombination, and S or G2/M checkpoint control. He is also interested in CtIP (also known as RBBP8) which functions together with the MRN complex to promote DSB resection and the generation of single-stranded DNA. Dr. Yuan worked on a newly identified human SWI5-MEI5 (C9orf119-C10orf78) complex which has an evolutionarily conserved function in HR repair. He also focuses on RPA associated proteins such as HARP (also known as SMARCAL1), mutations which are responsible for an autosomal recessive disorder known as Schimke immunoosseous dysplasia (SIOD). HARP can be recruited to stabilize stalled replication forks via its direct interaction with RPA, and therefore plays a role in maintaining genome stability.
Said Akli, Ph.D.
Dr. Akli’s research focuses on the role of cyclin E in breast and salivary tumorigenesis. When overexpressed in breast cancer cells, cyclin E induced genomic instability and resistance to p21, p27, and antiestrogens. LMW-E are tumor specific and are associated with the aggressive triple negative breast cancer. His current studies include generating transgenic mice using the doxycycline-inducible system to determine the requirement of LMW cyclin E for tumor maintenance and recurrence; identifying potential LMW-E/CDK2 substrates on a proteome-wide scale that could serve as novel therapeutic targets for the treatment of the aggressive LMW-E expressing triple negative breast cancer and identifying the salivary gland specific cyclin E-associated kinase that drives tumorigenesis in our mouse model of cyclin E-induced salivary gland cancer.
Lei Li, Ph.D.
Dr. Li is interested in molecular mechanisms of DNA damage repair and cell cycle checkpoint mechanisms, dubbed "care takers" and "gate keepers" for the maintenance of genome integrity. Dr. Li’s lab focuses on how DNA damage is sensed and transduced into checkpoint signals. A second area explores how chromatin remodeling mechanisms interact with DNA repair and damage checkpoint pathways, since the highly compacted chromatin structure needs to be reconfigured to allow access to DNA lesions. A third area deals with the repair of DNA interstrand cross-links, as many chemotherapy agents are bifunctional DNA cross-linkers that covalently join the two strands of the double helix. We have identified a recombination-independent and error-prone pathway for the repair of DNA interstrand cross-links. We are also investigating molecular mechanisms of Fanconi anemia, whose patient manifestations seem to reflect a deficiency in crosslink repair.
Li Ma, Ph.D.
he main goal of the Ma lab is to understand regulation of tumor invasion, metastasis, and epithelial-mesenchymal transition (EMT) by non-coding RNAs, and to design new therapeutic strategies. We have demonstrated the existence of metastasis-promoting and metastasis-suppressing miRNAs. Currently, my lab is working on four projects related to this topic: 1) We are dissecting the role of miR-10b in malignant progression using genetically engineered mouse models. 2) We are identifying the functional targets of metastasis-promoting miRNAs. 3) We are identifying and characterizing new epithelial-mesenchymal transition (EMT)-regulating miRNAs. 4) We are identifying lncRNAs that regulate EMT and metastasis. Collectively, the knowledge gained from these studies will fundamentally advance our current understanding of how miRNAs and lncRNAs regulate metastasis and EMT and may have important clinical implications.
Kathy Mason, M.Sc.
The Mason translational lab has conducted in-depth molecular, in vitro and in vivo investigations on chemoradiotherapy, particularly taxanes, and more recently on combining molecular targeting agents such as EGFR inhibitors (C225) and Cox 2 inhibitors, PARP inhibitors, WEE-1 inhibitors, and inhibitors of toll-like receptor 9 with radiotherapy. We have concentrated our investigations on cancers of the upper aerodigestive tract and head and neck cancers. Our laboratory expertise has contributed to the design and implementation of clinical trials having the potential to advance the standard of care. The Mason lab is at the forefront of normal tissue responses to cytotoxic insult and is on a quest for agents that can protect, mitigate, or treat radiation injuries sustained as a result of clinical exposure, radiation accidents, or radiation terrorism.
Marvin L. Meistrich, Ph.D.
Dr. Meistrich studies male germ cells and of the effects of radiation and chemotherapy. He uses mouse, rat, and non-human primate models, and has performed studies on semen samples collected from cancer patients, before, during, and after their therapy. He characterizes the survival of spermatogonial stem cells and their recovery after irradiation and different chemotherapeutic drugs, enabling selection of agents and doses to maximize future fertility potential. Although survival of the stem cells is essential for recovery of fertility, he showed, both in human and animal models, that damage to the somatic environment may cause prolonged azoospermia despite the presence of surviving stem cells.
Gunapala Shetty, Ph.D.
Disease Site(s): Effects of radiation on male reproduction and testicular cancer. Dr. Shetty is investigating hormonal manipulations to minimize the sterilizing effects of cancer therapeutic agents. He discovered that testosterone is inhibiting the differentiation of spermatogonial stem cells after cytotoxic treatment and is elucidating the mechanisms in rodent and non-human primate model using different hormone treatments, molecular targeting of testosterone responsive genes, genetic analysis and transplantation of stem spermatogonial cells. Another area of his interest is studying the mechanism of the radiation induction of testicular cancer during fetal life. Recently he had a surprising breakthrough that in a genetically susceptible mouse model radiation exposure at a specific period of fetal germ cell development dramatically induces testicular teratoma
Wei Zhou, Ph.D.
For male cancer patients, especially young ones, what adds to their misfortune is the loss of fertility due to irradiation therapy and/or chemotherapy. Spermatogenesis is a delicate process regulated precisely by hormones and temperatures. Thus, my major aim is to investigate the molecular mechanisms of hormones, including testosterone and estradiol, in the block and recovery of spermatogenesis after irradiation or toxicant exposure. I am hoping that our research could eventually lead to the development of clinical treatments which will help cancer patients regain their fertility and a happier life. Our research should also benefit other male patients that suffer from dysregulated hormone functions. Also, I am interested in investigating the roles of orphan nuclear receptor ERRβ in cancer chemoprevention.
Raymond E. Meyn, Ph.D.
The Meyn lab has two areas of interest; molecular targeted agents combined with radiotherapy and the role of the epithelial-to-mesenchymal transition (EMT) in governing tumor cell response to radiation. With respect to molecular targeted agents, we have shown that inhibitors of poly-(ADP)-ribose polymerase (PARP) and wee1 kinase have substantial radiosensitizing effects. Inhibitors of histone deacetylases (HDAC) and EGFR radiosensitize human tumor cells. Several of these strategies have been tested in clinical trials. With respect to the role of EMT in radiation response, model cell systems have shown that cells become radioresistant after undergoing EMT. Treatment of epithelial cells with TGF-beta or IL-6 converts them into mesenchymal cells and induces radiation resistance. The mechanism to explain this effect is under investigation but appears to involve an enhanced ability of mesenchymal cells to repair radiation-induced DNA double strand breaks.
Dr. Luka Milas, M. D., Ph. D., is professor of the Department of Experimental Radiation Oncology, the United Energy Resources, Inc. Professor in Cancer Research and Deputy-head for Translational Research of the Division of Radiation Oncology. Dr. Milas received his M.D. and Ph.D. degrees from the University of Zagreb in Croatia and his postdoctoral education and specialty training in radiation oncology at The University of Texas M.D. Anderson Cancer Center (MDACC). Since 1980, he has been professor of Experimental Radiation Oncology, and from 1980 to 2002 the chair of the Department of Experimental Radiation Oncology at M.D. Anderson. Throughout his career, his major research focus has been aimed at better understanding the biologic processes that govern tumor response to radiation and other cytotoxic agents and exploring new approaches to improving radio(chemo)therapy by enhancing tumor radio(chemo)response or by decreasing normal tissue toxicity. His research has largely been translational in nature, and many of his research findings have made their way into clinical trials at MDACC and worldwide. A hallmark of his studies has been its translational potential with a strong focus on rigorous investigation using in vivo models of tumor and normal tissue radiobiology. His studies on the action of chemotherapeutic drugs, such as taxanes and nucleoside analogs, or, more recently, molecularly targeting agents including EGFR, COX-2 and cdk inhibitors, in combination with radiotherapy point to the importance of what can be gained from these approaches and indicate mechanisms by which they might work in vivo. Knowledge of such mechanisms provides the biological rationale for the design of clinical trials and may identify the bases for individualization of patient treatment. Dr. Milas has published more than 400 original articles, reviews, and book chapters. Dr. Milas has served on the editorial boards of many journals, including the International Journal of Radiation Oncology, Biology, Physics, International Journal of Gastrointestinal Cancer, and Clinical Cancer Research. Dr. Milas has been active in a number of societies. He has served on the Tumor Biology Committee and the Finance Committee of the American Society for Therapeutic Radiology ond Oncology (ASTRO) and currently serves as vice chairman of the RTOG Tumor Biology and Translational Research Committee. He was a founding member of the Metastasis Research Society and has served as its secretary. Dr. Milas has served on numerous organizing committees of national and international scientific meetings. Dr. Milas has received many honors and awards. In 1997, he was elected as a corresponding member to The Croatian Academy of Sciences. Most recently, he received the 2004 Gold Medal Award from ASTRO, the largest radiation oncology society in the world, for his lifetime of meritorious achievements in translational research. The Gold Medal is the highest honor ASTRO bestows in recognition of distinguished accomplishments and contributions in the field of radiation oncology.
Jae-il Park, Ph.D.
The Park lab studies Wnt pathways in diverse contexts including cancer cells, embryonic stem cells, frog embryogenesis, mouse intestine and skin. Research on Wnt signaling in stem cell and cancer is being further developed into skin, colon and pancreatic cancer studies. A second area of interest is how telomerase is regulated in regeneration and disease.
Elizabeth L. Travis, Ph.D.
Dr. Travis’ research focuses on normal tissue complications of cancer treatments, the genetic basis of radiation induced pulmonary fibrosis, the mechanisms of radiation induce alveolitis, and the protection and mitigation of radiation injury in normal tissues.
Li Wang, M.D., Ph.D.
For radiation-induced normal tissue damage study, Wang’s research investigated mechanisms of radiation-induced lung fibrosis in mice with a focus on the role of transforming growth factor beta (TGF β) and its signaling pathway in development of fibrosis and the gene therapy of blocking TGF β signaling pathway. For exploration of new strategies to further improve the radiation therapeutic ratio, Wang studies molecular targeting in combination with radiotherapy and radio-chemotherapy. She is exploring the therapeutic efficacy of insulin-like growth factor 1 (IGF-1) receptor, poly-ADP-ribose polymerase (PARP), and integrin inhibitors on radiosensitivity of head and neck, lung and breast cancer cells growing in vitro, and on redioresponse of tumor xenografts (derived from these cell lines) growing in nude mice. She is also studying the radiosensitization effects and the mechanisms of cardiac glycosides.
Uma Raju, Ph.D.
My research interest is to test the hypothesis that targeting molecules whose functions are well regulated in normal cells but deregulated in cancer cells will improve tumor response with a better therapeutic gain. My research interest is to test the hypothesis that targeting molecules whose functions are well regulated in normal cells but deregulated in cancer cells will improve tumor response with a better therapeutic gain. My investigation include preclinical evaluation of several molecularly targeted agents: (1) cetuximab, (2) celecoxib, (3) flavopiridol, (4) BMS-599626 and BMS-690514, (5) XL-844, (6) Dasatinib (BMS-354825), (7) XL-228, (8) IMC-A12, and (9) Cilengitide. My focus is mainly on two sets of factors: (1) identification of cellular proteins and/pathways in DNA repair that are responsible for the resistant phenotype of cancer cells and (2) characterization of cancer stem cell markers that are involved in the resistance as well as recurrence and metastatic spread.