Robert F. Berman, Ph.D., Professor in the Department of Neurological Surgery and a member of the Center for Neuroscience. He is also affiliated with the M.I.N.D. Institute and is a member of the Center for Children’s Environmental Health. He is Director of Research for the Neurotrauma Research Laboratories at UC Davis. Dr. Berman is a member of the Executive Committee of the Neuroscience Graduate Program, and is also a member of the Pharmacology/Toxicology Graduate Program. Dr. Berman’s laboratory studies neurodevelopmental and neurodegenerative disease, with a focus on cellular mechanisms of brain injury associated with these disorders. A major research program is focused on the study of Fragile X-associated Tremor/Ataxia (FXTAS). FXTAS is a late developing neurodegenerative disease due to an expanded CGG trinucleotide repeat in the 5’-untranslated region of the FMR1 gene. This leads to the development of tremors, ataxia, neuropsychological problems including depression, and dementia in some patients. Ubiquitin staining intranuclear inclusions in neurons and astrocytes are pathophysiological hallmarks of FXTAS, and are shown in the Figure below. Dr. Berman’s laboratory is using transgenic CGG KI mice to model FXTAS and to understand the molecular mechanisms that underlie the neuropathology and neurobehavioral deficits in FXTAS. Both inducible and conditional mouse models are under development and study to determine which cells type (e.g., neurons versus glia) are critical to development of disease, as well as the potential for reversing the symptoms and progression of FXTAS by appropriate pharmacological or gene-targeted therapies. A second area of research examines the effects of neonatal toxin exposure (e.g., polybrominated diethyl ethers, PCB’s, ethanol) on brain development and behavior using animal models. His laboratory has recently developed a set of behavioral testing procedures to evaluate social behaviors and social interactions in rodents in order to provide useful models of for the study of neurodevelopment disorder, including autism. Finally, Dr. Berman’s laboratory is continuing research on the role of disruption of calcium homeostasis, and N-type voltage gated calcium channels in particular, in the pathophysiology and cell loss that occurs following traumatic brain injury. Dr Berman became a mentor of the CBST Summer Program in 2009 and he mentored one summer intern.
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Laura Borodinsky, Ph.D., Assistant Professor, Physiology and Membrane Biology
Institute for Pediatric Regenerative Medicine, Center for Neuroscience. Synaptogenesis is a multistep developmental process that relies on several events for its realization. Neurons need to produce the transmitter(s) that will enable them to communicate synaptically with other neurons or target organs. Axons must grow out and reach the appropriate target cells. Our lab is interested on understanding how these early events are shaped by electrical activity. We are interested in investigating the cellular and molecular mechanisms by which activity controls the development of the nervous system. Different forms of activity are present at early stages of development, substantially before synapse formation, suggesting that neuronal activity participates in early steps of differentiation. Neurotransmitter and neurotransmitter receptor specification, axonal pathfinding, synapse formation and function are some of the aspects of nervous system development we are currently studying. Other projects in the lab investigate the cellular and molecular mechanisms underlying neural tube formation. Our lab works on Xenopus laevis as a model system using a combination of methodologies including confocal microscopy, immunostaining, molecular biology, pharmacology and calcium imaging.
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Ting Guo, Ph.D., Associate Professor, Analytical and Physical Chemistry Professor, Department of Chemistry. Ting Guo's research group at UC Davis focuses on studying mechanisms of and the control of the energy flow between nanomaterials and between nanomaterials and their environment. The form of energy may vary from chemical energy to visible photon energy to x-ray photon energy. Nanomaterials can be uniquely used to harvest these forms of energy and direct them to facilitate chemical reactions including catalytic reactions, to create radicals in aqueous solution, and to produce local temperature rise. Most of these energy redirection and control processes can be made to occur to sub-ten nanometer nanomaterials. We therefore call these processes Redirecting Energy Flow using Nanomaterial Devices (REFUND) or Phenomena in Sub-Ten Nanometer Materials (PISTNM). Currently we are investigating high temperature catalysis using 1-nm nickel nanoparticles immobilized at the tips of single-walled carbon nanotubes (SWNTs), as well as enhanced x-ray radiation absorption and energy deposition using sub-ten nanometer gold nanoparticles. Dr Guo has mentored six summer interns in biophotonics related research.
Paul T. Henderson, Ph.D., Adjunct Assistant Professor, Department of Internal Medicine, UCD Medical Center. Dr. Henderson’s research interests include mechanisms of cellular response to oxidative stress, drug and carcinogen metabolism, pharmacokinetics assay development, mass spectrometry, HPLC. Dr. Henderson is pursuing the development of advanced diagnostics with the goal of predicting patient response to cancer drugs prior to initiation of toxic chemotherapy. The diagnostics development is enabled by accelerator mass spectrometry (AMS), an ultrasensitive technology for detecting rare isotopes such as radiocarbon and tritium in biological samples. AMS is also useful for measuring pharmacokinetics of small drug doses in humans, which Dr. Henderson is applying to drug development and drug formulation studies. Another project involves the incorporation of hydrophobic drugs and membrane proteins into nanoparticles made of apolipoproteins and phospholipids called nanolipoproitein particles (NLPs). NLPs closely mimic the cellular membrane bilayer, and render hydrophobic molecules water soluble. Dr. Henderson is using NLPs for drug delivery and protein biochemistry studies that are related to breast cancer research. Dr. Henderson has mentored two summer interns in biophotonics related research.
Pappanaicken Kumaresan, Ph.D., Assistant Professor, Division of Hematology/Oncology, UCD Medical Center. Dr. Kumaresan’s research interest include: (1) Pancreatic cancer specific ligands: Pancreatic cancer accounts for only 2% of all newly diagnosed cancers in the United States each year but it accounts for 5% of all cancer deaths. This is mainly due to the lack of early diagnostic markers for pancreatic cancer. In collaboration with Professor Kit Lam, chief Hematology/Oncology division, Internal Medicine Dept., UCDavis Medical Center and Dr. Anirban Maitra, Oncopathologist, Pathology department, John Hopkins University I am committed to find out pancreatic cancer specific peptide ligands which can be used for diagnostic and targeted therapeutic agents. One-bead-one-compound combinatorial chemistry libraries will be used to screen for therapeutic ligands. Currently, this work is supported by a RO3 grant. (2) Chemical antibodies: We are developing an immunotherapeutic agent by linking cancer specific targeting ligands with Fc portion of the human IgG. This will be a better agent not only to target cancer cells also to recruit the host immune system to clear the cancer cells. I am also interested to identify the bifunctional linkers to link tumor cells with NK cells, thereby increasing the tumor susceptibility for NK cell mediated lysis. In this respect, I have received two seed grants to identify the fusion proteins or linkers. This work is supported by "CML Research Program-DOD" for Innovator Award. Dr. Kumaresan has mentored six summer interns in biophotonics related research.
Kit S. Lam MD, PhD, Chief, Division of Hematology & Oncology, UCD Medical Center. Dr. Lam's research encompasses the development and applications of combinatorial chemistry to basic research, molecular imaging and drug development. On-going projects in his laboratory include the development of novel encoding techniques and screening methods for OBOC combinatorial libraries, development of cancer cell surface targeting agents for cancer therapy and in vivo imaging, applications of OBOC combinatorial library methods and chemical microarrays for cancer proteomics and enzyme profiling, development of label-free optical detection methods for chemical microarrays, development of imaging and therapeutic agents for Alzheimer’s disease, development of encoded OBOC combinatorial photoswitchable chemical libraries, development of peptide tags and corresponding optical imaging probes for multiplex optical imaging of cellular proteins in living cells, identification of substrates and development of inhibitors for protein kinases and proteases, development of novel glyco-markers for cancer diagnosis. Dr. Lam has mentored twelve summer interns in biophotonics related research.
Delmar Larsen, Ph.D., Assistant Professor, Department of Chemistry. The Larsen group focuses on exploring the ultrafast processes (fs to ns) of photoreceptors and other light sensitizing proteins which serve central roles in light activated biological functions. A fundamental, and yet unanswered, question for many photoreceptors is how the absorption of a photon by a small co-factor embedded within a protein is transformed into the complex response required for biological function. We explore how the surrounding protein modifies the chemistry of embedded photoreactions, including the evolving kinetics, reaction yields, thermodynamic and spectroscopic features with the aim of characterizing the hierarchy of reaction steps ranging from fastest local structural changes (femtosecond timescales) to slower long range conformational changes. This requires a multi-disciplinary research approach that incorporates tools from molecular biology, physical chemistry and computational sciences. Since 2008, Dr Larsen has mentored six summer interns in biophotonics related research.
Bruce Lyeth, Ph.D., Professor, Department of Neurological Surgery and member of the Center for Neuroscience. Dr. Lyeth’s laboratory uses a variety of cellular imaging techniques along with pharmacological, behavioral, and neuroanatomical, methods to investigate the cellular pathophysiological mechanisms involved in traumatic brain injury. The ultimate goal of this research program is to develop novel clinical therapeutic strategies targeted at reducing the debilitating consequences of traumatic brain injury in patients. Imaging techniques include brain culture live-cell fluorescence imaging to quantify intracellular ions in models of mechanical and neurochemical insults that reproduce many features of traumatic brain injury. Other imaging techniques include advanced stereological cell counts using light and epifluorescent microscopy, immunohistochemistry, and immunocytochemistry. Since 2007, Dr Lyeth has mentored four summer interns in biophotonics related research, one of them is now in STEM-related graduate school.
Laura Marcu, Ph.D. Professor, Department of Biomedical Engineering. Dr. Marcu’s research program has focused on the understanding of the biology of atherosclerosis. She has developed a catheter-based diagnostic technique for localization and characterization of rupture-prone atherosclerotic plaques. Specifically, she recently developed time-resolved laser-induced fluorescence spectroscopy (TR- LIFS) technique, which provides a direct evaluation of plaque composition, combined with high-resolution intravascular ultrasonography (IVUS) to create a visual reconstruction of plaque microanatomy. The resulting system enables the detection and monitoring of both compositional and structural features of atherosclerotic lesions which are predictive of plaque rupture. Since 2006, Dr. Marcu has mentored nine summer interns in biophotonics related research.
Lorena Navarro, Ph.D., Assistant Professor, Department of Microbiology. Our laboratory studies the molecular basis of bacterial pathogenesis in an area of study termed Cellular Microbiology, an exciting and rapidly expanding field that bridges the gap between molecular microbiology and host cellular biology. We are interested in defining virulence mechanisms with a specific emphasis on elucidating the biochemical and cellular function of bacterial effector proteins. We are using the Gram-negative bacteria Yersinia as a model system for studying the molecular events occurring at the host-pathogen interface. The genus Yersinia includes important human pathogens causing diseases ranging from bubonic plague to acute and chronic gastrointestinal disorders. Yersinia employ a sophisticated translocation apparatus, termed the type III secretion system, to deliver bacterial effector proteins directly into the host cytosol where they interface with eukaryotic signaling pathways and allow the pathogen to evade the host innate immune system, thus favoring survival of the bacteria. We are currently investigating the molecular function and cell biology of an essential Yersinia virulence protein, the Yersinia serine/threonine protein kinase YpkA (YpkA). By combining molecular, biochemical, cellular and genetic approaches in combination with human in vitro cell culture and murine in vivo model systems we hope to achieve the following goals: 1) define the biochemical mechanisms of novel toxins and effector proteins, 2) determine the physiological role of these virulent molecules to facilitate bacterial dissemination, innate immune evasion, and human disease progression, and 3) use this information to design therapeutic strategies aimed at effectively combating human infectious disease.
Tingrui Pan, Ph.D., Assistant Professor, Department of Biomedical Engineering. Dr Pan’s areas of research include the following: a) Innovative Micro-Nanofabrication Technologies. We keep seeking simple and creative solutions to manufacture 2D and 3D micro and nanoscale structures in an inexpensive and reproducible way. Learning from emerging technologies in both chemistry and electronics, we are extensively exploring novel top-down and bottom-up approaches to establish MEMS fabrication schemes for future biological and medical applications. b) Bio-Inspired Micro-Nano Electromechanical Systems. The field of bio-mimicry has attracted considerable attention recently. This is due to the ingenious ways in which nature has solved its evolutionary challenges through natural selection. We are particularly interested in transferring existing nature's designs into our micro-nano world development. Several bio-inspired designs are currently under the investigation, including biological attachment systems, micromotion systems, biophotonic systems, and biofluidics. c) Bioinstrumentations for Ophthalmic Diagnosis and Therapeutics. Wireless implantable micro-nanosystems are of particular importance in ophthalmology where the limited anatomical space requires miniature surgical instruments and implants. Our ongoing research focuses on design of bioinstrumentations, including implantable devices, for ophthalmic diagnosis and therapeutics. We are currently developing several novel clinical prototypes using flexible MEMS and electronics technologies. Dr Pan became a mentor of the CBST Summer Program in 2009 and he mentored one of the interns that was awarded one of the Best Presentation Award in the Summer Research Symposium.
Atul N. Parikh, Ph.D., Professor of Applied Science, Member of Biophysics, Biomedical Engineering, and Chemical Engineering & Materials Science Graduate Groups, Member of Biophotonics, Biotechnology Designated Emphases. Dr. Parikh’s research program encompasses physical science based studies of biologically relevant processes including self-assembly, molecular recognition, and signal transduction as applied to membrane organization, dynamics, and function. His program employs a broad suite of spatially- and temporally resolved imaging and spectroscopic probes at ultraviolet, visible, and infrared frequencies for interrogating and modulating these processes. Dr. Parikh has been successful in providing research opportunities for graduate students from several departments and graduate groups including Applied Science, Biophysics, Biomedical Engineering, Chemistry, Chemical Engineering & Materials Science, Electrical Engineering, and Mechanical Engineering. Dr Parikh has mentored ten summer interns in biophotonics related research.
Daniel A. Starr, Ph.D., Assistant Professor of Molecular and Cellular Biology, College of Biological Sciences. The Starr lab studies processes involved in the positioning of nuclei and other organelles to specific locations within a cell. In many cell types, including any polarized cell, the nucleus is positioned to a specific location. This is accomplished by two related processes: nuclear migration through the cytoplasm and anchorage of the nucleus to its proper position. Defects in nuclear envelope components and nuclear migration machinery lead to a variety of diseases including muscular dystrophy and lissencephaly. Despite the developmental importance of nuclear positioning, little is understood about how it is controlled. Starr’s work has demonstrated that several integral nuclear envelope proteins function to move the nucleus and to anchor it in place. The forward genetic approach in C. elegans has identified three conserved components of the nuclear envelope involved in nuclear positioning. ANC-1 consists of two actin-binding calponin domains, a huge central coiled domain, and a nuclear envelope targeting domain termed the KASH domain. Dr. Starr has mentored two summer interns in biophotonics related research and he is an active collaborator with the CBST Education Team.
Sebastian Wachsmann-Hogiu, Ph.D., Associate Professor in the Department of Pathology and Laboratory Medicine. Dr Wachsmann-Hogiu’s major research interest is centered on technology development and applications to the biomedical field and renewable energies and include: time-resolved Raman spectroscopy and imaging, plasmonics, Surface Enhanced Raman Spectroscopy (SERS), biosensors, fiber-based Raman endoscopes, point of care diagnosis, nonlinear microscopies, high-resolution microscopy and light conversion and energy storage. Dr Wachsmann-Hogiu has mentored five summer interns in biophotonics related research.
Min Zhao, Ph.D. Professor of Dermatology. Dr. Zhao’s group is interested in the control of directed cell motility and directed cell division. One particular interest is in the role played by small physiological electrical fields in wound healing, the development and regeneration of many tissues. He has been leading the group that attracted research funding of £2,7m (~ US$ 4.9 million) in the last eight years. He leads international collaborations to unravel the electrical control of cell migration and growth with Colin McCaig, John Forrester, Bing Song (University of Aberdeen), Josef Penninger (Austrian Academy of Sciences), Peter Devreotes (Johns Hopkins University Medical School), Henry Bourne (UCSF), Eammon Gaffney, Philip Manni (Oxford University), Robert Insall (Glasgow, Scotland), Kees Weijer (Dundee, Scotland), Yuesheng Huang and Jianxin Jiang (China). Steady extracellular electrical fields are present at a wound. Our group has used multiple approaches to study electric field-directed migration and growth of nerve, blood vessels, epithelial cells, and immune cells. Dr. Zhao proposed and initiated the work using the social amoeba Dictyostelium discoideum and transgenic animals to study the genetic basis of the effects and mechanisms of physiological electrical field. We use at molecule, cellular, tissue and whole animal level. Our recent publications that provide an overview of our work: Nature 2006; 442, 457-460. Trends in Neurosciences 2002;25, 354-359; Physiological Reviews. 2005; 85, 943-978.
