IDP ADVANCED CONCENTRATION IN
BIOCHEMISTRY & MOLECULAR BIOLOGY
Members of the BMB Concentration
THE ADVANCED CONCENTRATION IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
The Advanced Concentration in Biochemistry & Molecular Biology (B&MB) is comprised of faculty from the Department of Biochemistry and Molecular Biology, together with biochemists and molecular biologists from other College of Medicine departments. For the Fall 2009 incoming class, 15-20 of these faculty members will be actively recruiting new graduate students. Students in these laboratories will study a wide range of diseased-based research problems involving epigenetics, gene expression/ regulation, protein structure/function, enzyme mechanisms, membrane protein, DNA repair, and cancer biology. Upon completion of the degree, past graduates have had an outstanding record of obtaining academic positions or non-academic jobs in the pharmaceutical and biotechnology industries. Students who are interested in the Ph.D. degree in biochemistry and molecular biology can view individual B&MB faculty research interests at the Department (http://biochem.med.ufl.edu) or the B&MB IDP (http://idp.med.ufl.edu/ BMB/index.html) Web sites. The IDP home page (http://idp.med.ufl.edu/Pages/ Faculty.htm) has a complete listing of all faculty interested in having students join their laboratories.
First year IDP students have the opportunity to focus their studies within a specific Advanced Concentration at the start of the Spring semester. For the student who knows which discipline and/or Advanced Concentration interests them, this earlier focus will permit them to begin completing their core requirements of an Advanced Concentration during the first year. All graduate students in the College of Medicine IDP must enroll in the Fall semester interdisciplinary core curriculum (GMS 6001). For the Spring semester students who have decided on an Advanced Concentration or discipline can begin taking their specialized advanced modules/courses. Dr. Linda Bloom (email@example.com), Graduate Coordinator, will be available to provide guidance about course selection.
In the B&MB program, most students complete their coursework by the close of the second year, taking another two to three years to complete their research work. Records show that the average time required to complete the Ph.D. in any of the IDP concentrations varies by less than 6 months. The overall B&MB Advanced Concentration is designed to be flexible and allow the student to complete the classroom coursework as quickly as possible. Each student's program of study is individually designed to satisfy his/her scientific interests. Progress toward degree completion is overseen by a Supervisory Committee chosen by the student and mentor, which meets twice annually to help the student achieve maximal success in the laboratory.
EXAMPLES OF A FIRST YEAR CURRICULUM WITHIN THE B&MB ADVANCED CONCENTRATION STUDENT INTEREST: Molecular Biology or Epigenetics Didactic Credits 1st Year Fall
IDP Core Semester
1st Year Spring
BCH 6415 Advanced Molecular and Cell Biology Elective modules
3 credits 3 credits
Summer Year 1
2nd Year Fall
Three elective modules (BMB- Advanced Metabolism, Epigenetics, Advanced Gene Regulation) (genetics, virology, immunology, cell biol., etc.) Journal Clubs – Program specific-disciplined specific
Thesis Research 2nd Year Spring
Three elective modules (including IDP 1st yr modules from 6002) Journal Clubs
Thesis Research Summer Year 2
Thesis Research, prepare proposal, and take oral exam
STUDENT INTEREST: Structural Biology 1st Year Fall
IDP Core Semester
1st Year Spring
BCH 6740 Advanced Structural Biology Three elective modules
3 credits 3 credits
Summer Year 1
2nd Year Fall
Three elective modules (BMB-Advanced Metabolism, Spectroscopy, X-ray Crystallography) (neuroscience, immunology, cell biol., etc.) Journal Clubs – Program specific-disciplined specific
Thesis Research 2nd Year Spring
Three elective modules 3 credits (Structural Biology Techniques courses, Physical Biochemistry) Journal Clubs Thesis Research
Summer Year 2
Thesis Research, prepare proposal, and take oral exam
Recent Graduates and Current BMB Students Entering Class of 2001 Aaron Dossey (completed in Summer, 2006) Kim Aiken (completed in Summer, 2006) Omjoy Ganesh (completed in Spring, 2008) Patrick Quint (completed in Summer, 2006) Peng Liu (completed in Summer, 2006) Robyn Mayer (complete in Fall, 2006) Stephen Anderson (completed in Fall, 2006) Entering Class of 2002 Iman Al Naggar (completed in Spring, 2006) Jason Brant (completed in Spring, 2009) Jose Hernandez (completed in Spring, 2006) Zoe Fisher (completed in Fall, 2006) Valerie Davis (completed in Spring, 2007) Vijay Antharam (completed in Spring, 2008) Entering Class of 2003 Allyn Spear (completed in Summer, 2009) Antonette Bennett (completed in Summer, 2009) Jewell Walters (completed in Summer, 2009) Michele Thiaville (completed in Summer, 2008) Roxana Coman (completed in Summer, 2007) Shane Claggett (completed in Summer, 2008) Xiaolei Qiu (completed in Fall, 2008) Entering Class of 2004 Altin Gjymishka (completed in Fall, 2008) Zhuo Zhou Jesse Kay Justin Bickford Marsha Bush Melissa Marzahn (completed in Summer, 2009) Nan Su (completed in Fall, 2008) Suhasni Gopalakrishnan (completed Summer 09) Mina Hiona (completed in Summer, 2007) Ying Li Santhi Pondugula Carolina Pardo
Entering Class of 2005 Ada Ao Amanda Welch Brittney Whitaker John Domsic Entering Class of 2006 Balendu Avvaru Tolunay Beker Lisa Dyer Suznne Farver Dan Gibson Sujata Halder Sushama Kamarajugadda Kat Sippel Entering Class of 2007 Mukundh Balasubramanian Ankita Chiraniya Lauren Drouin Ryan Foster Kavitha Gnanasambandan Mollie Martin Robert Ng Lawrence Tartaglia Balasubramanian Venkatakrishnan River Ybarra Entering Class of 2008 Sarah Barilovits Jaclyn Hayner Joeva Hepburn Bhavitaben Patel Justin Runac Dayne West
Mavis Agbandje-McKenna, Ph.D. Professor, Biochemistry & Molecular Biology Using structural biology tools, namely Xray crystallography and cryo-electron microscopy, combined with other biophysical approaches, biochemistry and molecular biology, we study members of the Geminiviridae, Circoviridae, and Parvoviridae ssDNA virus families. The aim is to elucidate the roles of viral capsid and capsid protein structures in the dynamic array of biological processes occurring in the viral life cycle, from the initial stages of host infection to the delivery of genetic material into host cells and encapsidation of genomic DNA in viral progeny. We are also interested in understanding viral capsid adaptations that govern interactions with host immune machineries, especially mechanisms of host immune surveillance evasion and antibody neutralization. The ultimate goal is to develop disease treatments, in the form of capsid assembly disrupters, viral vaccines, foreign antigen delivery vehicles, and gene therapy vectors. AAV2
Capsid Structures of ssDNA Viruses
Professor Mavis Agbandje-McKenna received her Ph.D. in biophysics at the University of London in 1989 under the direction of Prof. Stephen Neidle for work on the biophysical characterization of a novel group of DNA-intercalating anthraquinone anti-tumor agents. She then joined Prof. Michael Rossmannâ€™s laboratory at Purdue University, Indiana, where she carried out research on structure to function correlation for the ssDNA Parvoviridae. In 1995, she joined the Department of Biological Sciences at the University of Warwick, England, UK, as an independent research fellow, where her research expanded to studies of the ssDNA Circoviridae and Geminiviridae. Dr. Agbandje-McKenna joined the Faculty at the University of Florida in 1999.
Linda B. Bloom, Ph.D. Associate Professor, Biochemistry & Molecular Biology
Our general research interests are in the dynamic protein-protein and proteinDNA interactions that are required to maintain the structure and to preserve the genetic integrity of DNA. We are working on defining molecular mechanisms by which the replication machinery duplicates genomes to support normal cell division, and defining mechanisms by which these enzymes respond to DNA damage that is encountered during replication. Although our current work is not directly aimed at developing a cure for a specific disease, basic research in the area of DNA replication provides the foundation of knowledge on which to make clinical correlations between defects in DNA replication and disease and on which to develop therapeutic agents targeted at the replication machinery of pathogens or cancer cells.
Associate Professor Linda B. Bloom earned her Ph.D. degree in organic chemistry from the University of Florida for her work on anabaseine. She joined Myron Goodmanâ€™s laboratory at the University of Southern California in 1990 where she used novel fluorescent techniques to study the fidelity of DNA replication. From 1996-1999, Dr. Bloom was an Assistant Professor of Chemistry & Biochemistry at Arizona State University. She joined the faculty in the Department of Biochemistry & Molecular Biology at the University of Florida in 1999.
Kevin D. Brown, Ph.D. Associate Professor, Biochemistry & Molecular Biology DNA damage initiates a series of signals that trigger responses such as activating cell cycle checkpoints and apoptosis. These pathways are crucial in maintaining stability of the human genome and limiting cancer development. One focus of the lab is studying how the kinases ATM and ATR function in damage response and how the mismatch repair system (MMR) impacts upon ATM/ATRdependent checkpoint and apoptosis signaling. Our lab determined that the alkylating agent MNNG triggers G2/M cell cycle arrest through MMRdependent activation of the kinases Chk1 and Chk2. Future studies will focus on understanding the function of ATM/ATR and MMR in response to this and other genotoxins. Another interest concerns our recent finding that the ATM gene is a novel target for epigenetic silencing via aberrant methylation of CpG dinucleotides within its proximal promoter. We are currently analyzing DNA samples taken from various human tumor types and studying the occurrence of ATM promoter hypermethylation using molecular genetics.
Associate Professor Kevin D. Brown earned his Ph.D. degree in Cell Biology at the University of Alabama-Birmingham in 1991 in the lab of Dr. Lester (Skip) Binder. He then joined Dr. Don Cleveland’s laboratory at Johns Hopkins where he worked on molecular mechanisms controlling chromosome migration and the cell cycle. In 1995 he joined Dan Tagle’s and Francis Collins’ group at the National Human Genome Research Institute/NIH where he began research on the function of the ATM kinase in the DNA damage response. In 1998 he took a position at LSU Health Sciences Center-New Orleans and rose to the rank of Associate Professor. He joined the the Department of Biochemistry and Molecular Biology at UF in 2004. Dr. Brown has served on NIH and DOD study sections and as a reviewer for numerous journals in the field.
Michael R. Bubb, M.D. Associate Professor, Dept. of Medicine The actin cytoskeleton provides the structural framework that maintains cell shape and facilitates cell motility, but it also organizes the cellular interior, creating a network for intracellular transport and communication. Our laboratory studies the complex and dynamic relationship between actin and the proteins that regulate the formation of actin polymer. Investigations focus on the cell biology & biochemistry of actin pertinent to apoptosis, angiogenesis, immunology, cancer biology, and neuroplasticity. We also study natural products that could be used as drugs to therapeutically manipulate actin polymer. Biophysical techniques, including timedependent fluorescence spectroscopy and analytical ultracentrifugation, are routinely utilized. Translational research studies of rheumatoid arthritis and osteoarthritis are in progress. The figure below depicts our success in crystallization of actin, leading to a novel hypothesis about the mechanism of actin polymerization.
Michael Bubb earned his M.D. degree at Johns Hopkins University in 1985. After studying Internal Medicine at Washington University in St. Louis, he did postdoctoral work with Dr. Edward Korn at the NIH, where he began his studies of the actin cytoskeleton and completed clinical training in arthritis and immunology. He joined the faculty of the University of Florida in 1994 and became an Associate Professor in 2000. Dr. Bubb was recipient of the Pfizer Scholar award in 1995, an NSF grant in 2004 and VA Merit Review Awards in 1998, 2001 and 2005. His scientific expertise crosses cell biology, biochemistry, natural product chemistry, biophysics, neuroscience and immunology. He is an editor for FEBS Letters, serves on the board of the cell biology section of the Faculty of 1000, and is director of graduate studies at the Malcom Randall VA Medical Center.
Jörg Bungert, Ph.D. Associate Professor, Biochemistry & Molecular Biology
We use a combination of genetic and biochemical approaches to analyze the structure and function of the human βglobin locus control region (LCR), a powerful regulatory genetic element located far upstream of the globin genes. The LCR, which is composed of several sub-regions revealing high sensitivity to nucleases in erythroid cells, provides an open chromatin structure over the entire globin locus and enhances globin gene transcription in a developmental stage specific manner. We use transgenic mice, embryonic stem (ES) cell differentiation systems, and in vitro assays to elucidate the mechanism by which the LCR regulates the recruitment of transcription and chromatin modifying complexes to the β-globin gene locus.
The Human β-Globin Gene Locus LCR
HS 5 4 3 2 1
>100 Kbp >60 Kbp
Yolk Sac Fetal Liver Bone Marrow
Jörg Bungert earned his Ph.D. degree in Molecular Genetics from PhilippsUniversity (Marburg, Germany) for his work on the characterization of erythroid specific transcription complexes under the direction of Klaus Seifart. In 1992, he joined Doug Engel’s laboratory in the Department of Biochemistry, Molecular Biology and Cell Biology at Northwestern University, where he studied the developmental regulation of the human β-globin genes. Dr. Bungert joined the faculty at the University of Florida in 1998.
Brian D. Cain, Ph.D. Professor, Biochemistry & Molecular Biology Research in the Cain lab centers on the structure, function and regulation of proton translocating ATPases. The primary project investigates the F1F0 ATP synthase of E. coli. Research focuses on the organization of the F0 subunits, the mechanism of proton conduction across the membrane, and the coupling of proton movement to ATP synthesis. We use a combination of site-directed mutagenesis, bacterial genetics and enzymology to look at the mechanism of enzyme function. The second project is a collaborative effort with Dr. Charles Wingo (Medicine) focusing on the mammalian renal H,KATPases. expression in animals and tissue culture cells.
Professor Brian D. Cain earned his Ph.D. in Cell Biology from the University of Illinois in 1983. His graduate work focused on phospholipid metabolism and cell cycle dependent assembly of the photosynthetic membranes of Rhodobacter sphaeroides. He was a postdoctoral fellow in Dr. Robert Simoniâ€™s laboratory at Stanford University. While at Stanford, he initiated studies on F1F0 ATP synthase which led to the recognition that the a subunit houses most of the F0 proton channel. In 1988, Dr. Cain joined the faculty of the University of Florida. His lab has demonstrated flexibility in the peripheral stalk of F1F0 ATP synthase. Dr. Cain served terms as Chairman of the NIH Physical Biochemistry Study Section and as a member of the Editorial Board of The Journal of Biological Chemistry.
Robert J. Cousins, Ph.D. Eminent Scholar, Food Science & Human Nutrition Our laboratoryâ€™s primary research emphasis involves the molecular and cell biology of zinc absorption, metabolism, function, and nutritional status assessment. Nutritional and physiological factors regulating expression of the zinc trafficking defense protein metallothionein and the zinc transporter gene families receive particular attention. Projects are aimed at the cellular or subcellular level, but animal models, including knockout mice, and human subjects are also used. Zinc-responsive genes are being identified using cDNA microarray analysis. Zinc transporter proteins are being characterized and their integrative regulation studied. Human zinc status assessment research uses microarray and quantitative RT-PCR technologies. Our overall research goal is to understand the biological significance of this essential micronutrient.
From Cousins et al., JBC 281:24085-24089, 2006
Robert J. Cousins holds the Boston Family Professorship of Human Nutrition. He received his Ph.D. in nutritional biochemistry from the University of Connecticut, and did postdoctoral research in vitamin D biochemistry with Hector DeLuca at the University of Wisconsin. Dr. Cousins has trained over 60 graduate students and postdoctoral fellows in both nutritional sciences and biochemistry. His research has been continuously supported by the NIH since 1972. He has served as president of both the Federation of American Societies for Experimental Biology and the American Society for Nutritional Sciences, associate editor of the Journal of Nutrition, and is currently Editor of the Annual Review of Nutrition. Dr. Cousins has won many university, national, and international awards, and is an elected member of the National Academy of Sciences.
Ben M. Dunn, Ph.D. Distinguished Professor, Biochemistry & Molecular Biology The research of my lab is focused on understanding the specificity of the proteolytic enzymes. Much of our work has been done on enzymes from the malaria parasite, Plasmodium falciparum, and the retroviral enzymes such as HIV and FIV PRs. We utilize site-specific mutagenesis as well as domain exchange to ascertain the effect on catalysis, and obtain structural information via crystallography or NMR. Given that we must have pure samples of fully functional proteins and because we are working with many mutant forms of recombinant proteins, we frequently solve problems to optimize protein folding. Our work on active site specificity has proved valuable in the process of drug design for targets involved in infectious diseases. Ph.D. students from our lab are employed in major pharmaceutical companies and universities. [Below: Detail of active site of PfPM2 with bound inhibitor designed in the Dunn lab.]
Professor Ben M. Dunn worked with Thomas C. Bruice at the University of California Santa Barbara on the mechanism of lysozyme and earned his Ph.D. in Chemistry in 1971. He examined the mechanism of nucleases as a Postdoctoral Associate and a Staff Research Fellow with Christian B. Anfinsen at the NIH. Dr. Dunn joined the Faculty at the University of Florida in 1974 and rose to the rank of Professor in 1986. He has won the College of Medicine Faculty Research Prize and became a Distinguished Professor in 1998. Dr. Dunn has served on many NIH review panels and is Editor-in-Chief of Protein and Peptide Letters and Current Protein and Peptide Science.
Arthur S. Edison, Ph.D. Associate Professor, Biochemistry & Molecular Biology
The Edison laboratory is interested in chemical signaling and communication. Most of our research involves NMR spectroscopy, natural products chemistry, Caenorhabditis elegans, and molecular biology. We have developed very highsensitivity NMR methods to analyze small amounts of material. We are developing approaches to analyze complex biological mixtures of small molecules like metabolites and pheromones. We currently have two main projects in these areas, the discovery of C. elegans chemical ecology and the analysis of chemical variability in the venom of walkingstick insects. The major goal of the C. elegans project is to isolate and identify small molecules that the nematodes use for communication. This will increase our understanding of chemical communication in general and will provide potential new leads for parasitic nematode control.
We recently discovered that the 4 molecules above act as mating pheromones at low concentrations but induce a dormant â€œdauerâ€? state at higher concentrations. Srinivasan, Kaplan, et al., Nature 454, 11151118 (2008).
Arthur S. Edison completed his Ph.D. in biophysics from the University of Wisconsin-Madison where he developed and applied NMR methods for protein structural studies under the supervision of John Markley and Frank Weinhold. In 1993, Dr. Edison joined the laboratory of Antony O. W. Stretton at the University of Wisconsin as a Jane Coffin Childs postdoctoral fellow where he investigated the role of neuropeptides in the nervous system of the parasitic nematode Ascaris suum. He joined the faculty at the University of Florida in 1996. Dr. Edison is the recipient of the 1997 American Heart Association Robert J. Boucek Award and of a CAREER Award from the National Science Foundation in 1999.
James B. Flanegan, Ph.D. Professor & Chairman, Biochemistry & Molecular Biology RNA viruses cause a variety of diseases including poliomyelitis, hepatitis, the common cold, encephalitis, etc. We use poliovirus as a model system to study the molecular basis of (+)-strand RNA virus replication. Using cell-free translationRNA replication reactions, we synthesize authentic progeny RNA and infectious virus in vitro. This approach has allowed us to characterize the biochemical activities of the viral proteins and to identify cis-active replication elements in the viral genome. We are now investigating how the viral proteins and these cis-active sequences interact to regulate the translation, replication, recombination and stability of viral RNA. Our results suggest that the ends of the viral genome interact to form a circular RNP complex that regulates the viral RNA replication cycle (see model). Since other (+) strand RNA viruses utilize similar replication strategies, we are now adapting this system for use with other RNA viruses such as hepatitis C virus. Initiation of Poliovirus Negative-Strand RNA Synthesis
Professor and Chairman James B. Flanegan earned his Ph.D. degree in Biochemistry at the University of Michigan in 1975 for his work with Dr. G. Robert Greenberg on bacteriophage T4 DNA replication. In 1975, he joined Dr. David Baltimoreâ€™s laboratory at MIT where he began his research on the replication of RNA viruses. He joined the faculty of the University of Florida in 1978 and rose to the rank of Professor in 1987. In 1998, he was named Chair of the Department of Biochemistry and Molecular Biology. Dr. Flanegan has served as a member of the NIH Virology Study Section and the Editorial Boards of Virology and the Journal of Virology. He was awarded the College of Medicine Faculty Research Award in 1989, the University of Florida Research Foundation Professorship in 1998 and the Professorial Excellence Program (PEP) Award in 1999.
Susan C. Frost, Ph.D. Professor, Biochemistry & Molecular Biology My laboratory studies the regulation of glucose transport in adipocyte and mammary carcinoma cells. In adipocytes, we hypothesize that a novel protein interacts with the GLUT1, glucose transporter in lipid rafts to enhance glucose uptake in response to nutrient deprivation. Lipid rafts are cholesterolrich plasma membrane domains that serve as signaling platforms for a number of pathways. We are using molecular approaches to identify this protein which may provide a therapeutic target in insulin resistant (type II) diabetics. In breast cancer cells lines, we are interested in the role of cellular acidification in response to hypoxia. Hypoxia induces GLUT1 whose activity contributes to acidification by converting glucose to lactic acid. Carbonic anhydrase IX is also upregulated and we hypothesize that its activity contributes to acidification by converting extracellular carbon dioxide to bicarbonate and a proton. We are currently testing expression of CA family members and specific inhibitors of CAIX to determine its role in metastatic potential.
Zoe Fisher, 2005
Dr. Susan C. Frost earned her Ph.D. degree in biochemistry from the University of Arizona in 1979. She was an Adjunct Assistant Professor at Arizona for three years where she studied lipid metabolism in neonates. In 1982, she took a postdoctoral fellowship in the laboratory of M. Daniel Lane at Johns Hopkins University where she studied insulin action on glucose transport in adipocytes. Dr. Frost joined the Faculty at the University of Florida in 1985. She served on the Editorial Board of the American Journal of Physiology from 1992 to 2001. Dr. Frost chaired the Department of Biochemistry and Molecular Biology from 1996 to 1998. She has served as an Ad Hoc reviewer for Endocrinology study section and a member of several special advisory committees to the NIH. Currently, she is the Director of the Advanced Program in BMB.
Steven C. Ghivizzani, Ph.D. Associate Professor, Orthopaedics and Rehabilitation Our work is translational in nature in that we are developing effective gene-based treatments for musculoskeletal disorders. By delivering cDNAs encoding therapeutic proteins to cells at sites of disease, we can convert these cells into factories for sustained, localized protein synthesis and secretion. Our primary targets are arthritis and tissue repair. For arthritis, using recombinant adenovirus, adeno-associated virus and lentivirus we are working to stably insert therapeutic genes into cells in articular tissues to enable the persistent localized production of anti-inflammatory proteins within diseased joints. Toward tissue repair, we are developing strategies to enable the sustained synthesis of growth factors, morphogens and transcription factors within damaged tissues to stimulate mesenchymal stem cells toward specific differentiation pathways. Methods are being explored to improve synthesis of repair tissues for cartilage, bone, ligament and tendon. Gene Therapy for Arthritis
Steve Ghivizzani, earned his Ph.D. in Immunology and Medical Microbiology at UF in 1991 in Dr. William Hauswirthâ€™s laboratory where he studied mitochondrial DNA replication and transcription. As a post-doc he joined the laboratories of Drs. Paul Robbins and Christopher Evans at the University of Pittsburgh where he performed research in gene therapy for musculoskeletal disorders. He was instrumental in the implementation of the first clinical trial of a gene therapy for a non-fatal disease. After a stint in the biotech industry, in 1999 he was recruited to Harvard Medical School as an Assistant Professor in the Center for Molecular Orthopaedics. In 2004, he returned to the University of Florida to join the faculty as an Associate Professor in the Department of Orthopaedics and Rehabilitation.
Suming Huang, Ph.D. Assistant Professor, Biochemistry and Molecular Biology Epigenetic modifications play an important role in chromatin organization and gene expression. Perturbation of this process often leads to cancer. My lab is interested in understanding the epigenetic mechanism that underlies the controls of the enhancer and promoter interaction during transcriptional activation. We are currently focusing on examining the epigenetic mechanisms by which the chromatin insulator binding factor USF1 maintains a local environment of active chromatin, both by biochemical and functional analysis of the USF1 associated histone modifying enzyme complexes. We are also studying the effects of these complexes on histone modification patterns, local and long-range chromatin structure, and transcriptional regulation. Another project that my lab is focusing on is the transcriptional regulation of TAL1/SCL, which plays a critical role in normal and malignant hematopoiesis. Activation of TAL1 is the most frequent gain-of-function mutation occurred in T-cell lymphoblastic leukemia (T-ALL). We will use biochemical and cell biology approaches such as protein purification, siRNA knockdown, tissue culture, ChIP-Seq, ChIP, microarray, and in vitro and in vivo transformation assays to determine: 1) the mechanism that triggers the ectopic activation of TAL1 transcription in T-ALL, and 2) the mechanism that dictates the TAL1 transcriptional activity in normal and malignant hematopoiesis.
Dr. Suming Huang received his PhD in Molecular Virology from Mississippi State University in 1996. He then joined Dr. Stephen Brandtâ€™s laboratory at Vanderbilt Medical Center as a postdoctoral fellow, where he worked on the transcriptional regulation of hematopoiesis. In 2001, he joined Gary Felsenfeldâ€™s group at NIDDK/NIH to study the chromatin insulator and epigenetic regulation of chromatin structure and gene expression. Dr. Huang joined the faculty at the University of Florida in 2006.
Michael S. Kilberg, Ph.D. Professor, Biochemistry and Molecular Biology We are investigating transcriptional and epigenetic regulation of several human genes in response to nutrient stress; either protein/amino acid deprivation, which activates the Amino Acid Response signaling pathway or ER stress, which activates the Unfolded Protein Response pathway. For example, genomic analysis of the human asparagine synthetase (ASNS) gene has allowed us to identify several genomic cis-acting sequences, the corresponding transcription factors, and the assembly mechanisms of the general transcriptional machinery that are responsible for nutrient-dependent transcriptional control. These data have led us to focus on the molecular control of the genes for the nutrient-responsive transcription factors themselves, to understand the mechanisms for “regulation of the regulators.” Among these transcription factors are ATF4, ATF3, C/EBPβ, JUN, FOS, and NFkB. Model for Transcriptional Control of the Human ASNS Gene
Professor Michael S. Kilberg has received the University of Florida Doctoral Advisor/Mentoring Award, the highest graduate student mentoring award given by UF. Dr. Kilberg earned his Ph.D. in biochemistry and molecular biology for work on membrane transporters. He did post-doctoral studies at the University of Michigan, before joining the faculty at UF in 1980. He has written numerous reviews, organized several international symposia, and written multiple chapters for both the Annual Review of Nutrition and the Annual Review of Biochemistry. Dr. Kilberg has served three terms on the Editorial Board of the Journal of Biological Chemistry. He was awarded the 1992 College of Medicine Faculty Research Award and a University of Florida Research Foundation Professorship in 1997.
Michael P. Kladde, Ph.D. Associate Professor, Biochemistry & Molecular Biology
Associate Professor Mike Kladde earned his Ph.D. degree in Cellular and Molecular Biology with Dr. Jack Gorski at the University of Wisconsin-Madison in 1991 on estrogenic regulation of gene expression. He then pursued postdoctoral work on chromatin structure and function in the laboratory of Dr. Robert T. Simpson at the National Institutes of Health and then at The Pennsylvania State University. Dr. Kladde took a position at Texas A&M University in 1998 and rose to the rank of Associate Professor continuing his studies on activation of gene expression in the context of chromatin. He joined the Department of Biochemistry and Molecular Biology at UF in 2007. Packaging DNA into chromatin comprised of repeating nucleosomes regulates all DNA-based functions in eukaryotes. One emphasis of the lab is on studying how chromatin is disassembled or remodeled to activate transcription. These studies focus on a proven model system, the PHO5 promoter in the budding yeast, S. cerevisiae. Yeast offers many experimental advantages, including ease in biochemical, genetic, and molecular approaches. Another area of investigation concerns the role of epigenetic or post-replicative methylation of DNA in tumor progression. In a recent collaboration, we have discovered increased DNA methylation of a novel mammalian tumor suppressor gene that is associated with elevated invasiveness of breast cancer. Future studies will examine mechanisms of epigenetic silencing of this tumor suppressor in human breast cancer lines and patient tumor tissue. Both areas of study take advantage of our powerful population and single-molecule strategies (MAP and MAP-IT, respectively) for probing chromatin structure with DNA methyltransferases.
Philip J. Laipis, Ph.D. Professor, Biochemistry & Molecular Biology My lab studies replication and integration of Adeno-Associated Virus (AAV), structure/function of carbonic anhydrase (CA), and gene therapy for phenylketonuria (PKU). AAV, a small DNA virus, requires co-infection with helper virus for replication. Without helper, AAV integrates into human chromosome 19. My lab is defining the cellular requirements for AAV replication and integration, as well as characterizing the AAV Rep protein. My lab has cloned nine mammalian CA genes and made many amino acid mutations. This work has allowed us to analyze structure-function relationships, especially proton transfer. Experiments leading to a CAIII knockout mouse and isozyme specific inhibitors are in progress. Finally, my laboratory has cloned the gene for phenylalanine hydroxylase (PAH), developed AAV-based vectors expressing PAH, and successfully cured PKU in the PAHEnu2 mouse model. The ultimate goal is human clinical trials.
Humancarbonic anhydrase II. Catalytic histidine residues are depicted in yellow.
Professor Philip Laipis received the Ph.D. in genetics from Stanford University in 1972. His thesis research with Dr. A.T. Ganesan examined the role of DNA polymerases and DNA ligase in repair and recombination of B. subtilis DNA. He joined A.J. Levineâ€™s laboratory at Princeton University as an NIH postdoctoral fellow, and he studied replicating SV40 viral DNA. He joined the University of Florida in 1974. He rose to the rank of Professor in 1986. Dr. Laipis has served on the NIH Physiological Chemistry Study Section and since 1997 has been the Associate Chair of the Department.
Joanna R. Long, Ph.D. Associate Professor, Biochemistry & Molecular Biology Our research focuses on the relationship between proteins and their environment in mediating the properties of specialized tissues. My lab uses a combination of biophysical techniques, functional assays (in collaboration with other research groups at UF), and solid state NMR experiments to address three research areas: 1) We are funded by the NIH to study the structure and dynamics of lung surfactant peptides interacting with lipids found in the lung; 2) We are studying the ion channelforming M2 segments of the nicotinic acetylcholine receptor (nAChR) to yield insights into key features of aging-related changes in membrane composition that affect the function and regulation of ion channel gating; 3) We are exploring the molecular level interactions of bone sialoprotein II with hydroxyapatite and collagen and examining the regulation, through phosphorylation, of BSP in mineralizing tissue. We also work on developing solid state NMR methodologies. Protein Regulation of Lipid Dynamics
Joanna R. Long received her Ph.D. in Physical Chemistry from the Massachusetts Institute of Technology in 1997 for work done in the laboratory of Dr. R. G. Griffin on applying solid state NMR techniques to the study of peptide and lipid structure and dynamics. She then joined the laboratory of Dr. Pat Stayton at the University of Washington, in collaboration with Dr. Gary Drobny, to do postdoctoral research studying protein structure and dynamics at mineral and polymer interfaces for tissue engineering applications. In 2000, she joined the Department of Chemistry at the University of Washington as Director of the NMR Facility. Dr. Long joined the Faculty at the University of Florida in 2002.
Jianrong Lu, Ph.D. Assistant Professor, Biochemistry and Molecular Biology
Our major research interest is aimed at understanding the molecular mechanisms underlying tumor development and progression, and exploring knowledge-based anticancer therapeutic opportunities. Current study focuses on epigenetic regulation of cancer metastasis. In particular, we investigate specific transcription factors and chromatin modifications critically involved in tumor angiogenesis, epithelialmesenchymal transition, and cancer stem cells.
Dr. Lu received his Ph.D. from the University of Texas Southwestern Medical Center at Dallas in 2000 in the laboratory of Dr. Eric Olson. His graduate work focused on transcriptional regulation of muscle development and diseases. He then joined Dr. Philip Leder's group as a postdoctoral fellow at Harvard Medical School, where he began studies on cancer biology. Dr. Lu joined the Department of Biochemistry and Molecular Biology at the University of Florida in 2005.
Thomas H. Mareci, Ph.D. Professor, Biochemistry & Molecular Biology Dr. Mareci studies tissue structure and biochemical processes in the nervous system of living organisms using nuclear magnetic resonance (NMR). His current projects are: 1) Develop and apply diffusion-weighted imaging to map fiber tracts in highly structured white and gray matter of nervous tissue. 2) Study convection drug delivery, using dynamic contrast enhanced MR imaging, and model the kinetics of drug distribution affected by tissue barriers. 3) Design implanted NMR coils that are inductively coupled to an external coil during measurements. These coils allow the acquisition of very high spatial-resolution MR images and spectra in vivo. Future work will be directed toward NMR measurements in vivo of the neurochemical profile of the brain for the study of epilepsy. His students come from diverse disciplines: biomedical and electrical engineering, chemistry, neuroscience, and physics.
Diffusion image of brain fiber structure (Mareci)
Professor Mareci received a doctoral degree in physical chemistry in 1982 from Oxford University for his work on nuclear magnetic resonance multiplequantum spectroscopy. Dr. Mareci joined the faculty of the University of Florida in 1982 and served as the Director of the Center for Structural Biology from 1993-2007. He is an affiliate faculty member of the Departments of Physics and Biomedical Engineering and a member of the National High Magnetic Field Laboratory, where he is helping to develop the in vivo magnetic resonance program. He has published over 60 journal articles and 11 book chapters.
Robert McKenna, Ph.D. Associate Professor, Biochemistry & Molecular Biology
My research interests are focused on interpreting how the structure of a biological molecule plays a role in its function. We use the techniques of Xray and neutron crystallography and insilico modeling to obtain 3D structural information and correlate this to mutational, kinetic, and biochemical data. The result is a structural map of the biological molecule in the context of its function . The goals of these studies are 1) to understand the mechanism of how the system works, and 2) to develop therapeutic strategies of treatments of human diseases attributed to these targeted biological molecules. Current studies include: Carbonic anhydrases, manganese superoxide dismutase, HIV-protease, malariaplasmepsins, the cancer-associated Mycoplasma hyorhinis protein Mh-p37.
Associate Professor Robert McKenna received his Ph.D. in crystallography at the University of London in 1989 under the direction of Prof. Stephen Neidle for work on structural studies of nucleic acid targeted anti-cancer drug design. He then joined Prof. Michael Rossmannâ€™s laboratory at Purdue University, Indiana, where he carried out research on structure to function correlation for ssDNA virus capsids. In 1995, he joined the Department of Biological Sciences at the University of Warwick, England, UK, as a research fellow, where he continued his research on structure-function analysis of virus capsids. Dr. McKenna joined the Faculty at the University of Florida in 1999.
Harry S. Nick, Ph.D. Professor, Neuroscience
Our laboratory studies the molecular mechanisms that control gene expression during acute inflammatory events. Research has focused on proteins that exhibit both pro-and anti-inflammatory activities in the lung, central nervous system and the kidney. These genes include: manganese superoxide dismutase (MnSOD), a potent anti-apoptotic antioxidant enzyme; cytosolic phospholipase A2 (cPLA2), the first step in prostaglandin and leukotriene biosynthesis; microsomal prostaglandin E synthase, the enzyme that synthesizes one of the most physiologically potent eicosanoids, PGE2 and heme oxygenase-1 (HO-1), the primary enzyme in heme metabolism. Our efforts include state of the art molecular biology approaches to understand the underlying events that orchestrate gene regulation. Our laboratory is also actively developing strategies for gene delivery specifically targeted to diabetes, asthma, inhibition of cancer growth and events associated with acute spinal cord injury.
Dawn Beachy Model of the MnSOD intronic enhancer-promoter and some trans-acting factors that mediate gene induction by inflammatory cytokines.
Professor Harry Nick earned his Ph.D. in chemistry from the University of Pennsylvania (1982) working with Dr. Ponz Lu on protein-DNA interactions using high resolution NMR spectroscopy. As a postdoctoral fellow with Dr. Walter Gilbert at Harvard University, Dr. Nick helped develop in vivo footprinting methodology for the molecular analysis of cytosine methylation and detection of proteinDNA interactions in vivo. He joined the University as an Assistant Professor in 1985 and became a full Professor in 1997. He served as a charter member of the NIH Lung Biology Study Section and recently received a MERIT award from the NIH. He is also currently the Associate Director of the McKnight Brain Institute.
Daniel L. Purich, Ph.D. Professor, Biochemistry & Molecular Biology Molecular Motors in Actin-Based Motility A specialist in enzyme chemistry and cell motility, Dr. Purich has published over 150 papers, chapters, and review articles on the mechanisms of action of enzymes, microtubules, and actin filaments. To account for noncovalent substrate- and product-like states of mechanoenzyme reactions (e.g., State1 + ATP = State2 + ADP + Pi), he redefined enzyme catalysis as the facilitated making/breaking of chemical bonds - not just covalent bonds. He also coined the term energase to signify those energy-driven enzymes (e.g., molecular motors, active transporters, translocators, GTPregulatory proteins, ribosomes, etc.) comprising a hitherto unrecognized seventh and distinct class of enzyme-catalyzed reactions. He and UF colleague Richard Dickinson co-discovered actoclampin, an entirely novel class of molecular motors that harness the Gibbs energy of ATP hydrolysis as they track along actin filament (+)-ends and generate the substantial forces needed for amoeboid-like cell crawling, endosome and phagosome motility, as well as dendritic spine remodeling into functional synapses
Dr. Purich earned his Ph.D. for investigating brain hexokinase kinetics and regulation under Herbert Fromm at Iowa State University. A Staff Research Fellow under Earl Stadtman at the NIH, he elucidated the enzyme nucleotidylation cascade controlling bacterial glutamine synthetase. Purich joined the University of California Santa Barbara Department of Chemistry in 1973, and rose through the ranks to full professor in 1982. While at UCSB, he was awarded an A. P. Sloan Award, the. Plous campus-wide teaching award, and a NIH Research Career Development Award. In 1984, he became Chairman of Biochemistry & Molecular Biology here and resumed full-time professorial activities in 1996. Dr. Purich served on the editorial boards of Journal of Biological Chemistry and Archives of Biochemistry & Biohysics, served on the NIH Biochemistry Study Section, and edited the six-volume Enzyme Kinetics & Mechanism series in Methods in Enzymology, as well as Contemporary Enzyme Kinetics & Mechanism. Dr. Purich is the lead author of The Handbook of Biochemical Kinetics (2000) and The Enzyme Reference (2002), His latest book Modern Enzyme Kinetics: Principles & Practices will appear in Spring, 2009.
Gregory S. Schultz, Ph.D. Professor Obstetrics and Gynecology Growth factors, cytokines and proteases play key roles in regulating wound healing. The cost of chronic wounds that fail to heal, or wounds that heal with excessive scar is over $4 billion/year in the US. My lab uses biochemical approaches to identify and understand the molecular imbalances that prevent wounds from healing or stimulate excessive scar formation, then translates that understanding into new clinical therapies that selectively identify and correct the biochemical abnormalities. Our analyses of biopsies and wound fluids have revealed that chronic, nonhealing wounds have bacterial biofilms that induce sustained, elevated levels of inflammatory cytokines (TNFα, IL-1β), and proteases (MMPs) that destroy proteins that are essential for healing (growth factors, receptors and ECM proteins). These data have led to our development of a rapid, point-of-care detector for MMPs and ongoing clinical trials of topical treatment of diabetic foot ulcers with protease inhibitors. Our biochemical analysis of fibrotic scars established the prolonged elevated activity of two growth factors, transforming growth factor beta (TGF-β) and connective tissue growth factor (CTGF) are primarily responsible for causing excessive scarring and fibrosis. We are developing antisense oligonucleotides, siRNAs, and ribozymes that selectively target TGF-β and CTGF mRNAs. We are also part of a collaborative team developing ribozymes that inhibit Herpes virus replication, for which the ultimate clinical goal is permanent treatment for corneal and genital herpes infections.
Professor Schultz received a Ph.D. in Biochemistry from Oklahoma State University in 1976 in the area of endocrine regulation of breast cancer. He then completed 3 years of post-doctoral training in cell biology at Yale investigating angiotensin II receptors of vascular smooth muscle cells. In 1979, he joined the Department of Biochemistry at the University of Louisville and developed a research program on growth factor regulation of cancer cell growth and wound healing. In 1989, he was appointed Professor of Obstetrics and Gynecology at the University of Florida and established the Institute for Wound Research. Dr. Schultz has 250 publications with over 6,500 citations, is an editor for six journals, and continuously funded by NIH and biotech companies. He was President of the Wound Healing Society (1999-2001), received a Medicinae Doctorem (hc) from Linkoping University, Sweden, the UF Professorial Excellence Program (PEP) Award, the UF International Educator Award, and COM Basic Science Research Award (2008).
Thomas P. Yang, Ph.D. Professor, Biochemistry and Molecular Biology
Our laboratory studies the regulation of transcription, particularly epigenetic mechanisms that regulate activation and silencing of mammalian genes. We employ two genetic systems of monoallelic gene expression: mammalian X chromosome inactivation, inactivation, and genomic imprinting in the Angelman/Prader-Willi syndrome region of human chromosome 15 and mouse chromosome 7. In each system, both a transcriptionally active and inactive allele of a given gene reside within the same nucleus. We are interested in the mechanisms by which these systems of differential gene expression are established and maintained during mammalian development. Our current studies focus on the roles of DNA methylation and chromatin structure in regulating transcription using mouse genetic models.
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Dr. Yang received his A.B. degree from from Cornell University and his Ph.D. in in Molecular Biology and Biochemistry from the University of California, Irvine. Irvine. As a postdoctoral fellow, he studied medical and human molecular genetics with Dr. C. Thomas Caskey at the Baylor College of Medicine, and transcriptional regulation with Dr. Arthur Arthur D. Riggs at the Beckman Research Institute of the City of Hope. Dr. Yang joined the Dept. of Biochemistry and Molecular Biology in 1988 and rose to the rank of Professor in in 1999. He also serves as the Program Director of the Center for Mammalian Genetics, is a member of the American Cancer Society, Florida Division, Peer Review Committee, and was a member of the National Institutes of Health Biological Sciences-1 Study Section.
BMB Concentration Members