Dr. LaPlaca’s broad research interests are in neurotrauma, injury biomechanics, and neuroengineering as they relate to traumatic brain injury (TBI). The goals are to better understand acute injury mechanisms in order to develop strategies for neuroprotection, neural repair, and more sensitive diagnostics. More specifically, the lab studies mechanotransduction mechanisms, cellular tolerances to traumatic loading, and plasma membrane damage, including mechanoporation and inflammatory- & free radical-induced damage. We are coupling these mechanistic-based studies with –omics discovery in order to identify new biomarker candidates. In addition, Dr. LaPlaca and colleagues have developed and patented an abbreviated, objective clinical neuropsychological tool (Display Enhanced Testing for Cognitive Impairment and Traumatic Brain Injury, DETECT) to assess cognitive impairment associated with concussion and mild cognitive impairment. An immersive environment, coupled with an objective scoring algorithm, make this tool attractive for sideline assessment of concussion in athletic settings. Through working on both basic and clinical levels she is applying systems engineering approaches to elucidate the complexity of TBI and promoting bidirectional lab-to-clinical translation.
All organisms use chemicals to assess their environment and to communicate with others. Chemical cues for defense, mating, habitat selection, and food tracking are crucial, widespread, and structurally and functionally diverse. Yet our knowledge of chemical signaling is patchy, especially in marine environments. In our research we ask, "How do marine organisms use chemicals to solve critical problems of competition, disease, predation, and reproduction?" Our group uses an integrated approach to understand how chemical cues function in ecological interactions, working from molecular to community levels. We also use ecological insights to guide discovery of novel pharmaceuticals and molecular probes.
In collaboration with other scientists, our most significant scientific achievements to date are: 1) characterizing the unusual molecular structures of antimicrobial defenses that protect algae from pathogens and which show promise to treat human disease; 2) understanding that competition among single-celled algae (phytoplankton) is mediated by a complex interplay of chemical cues that affect harmful algal bloom dynamics; 3) unraveling the molecular modes of action of antimalarial natural products towards developing new treatments for drug-resistant infectious disease; 4) discovering that progesterone signaling and quorum sensing are key pathways in the alternating sexual and asexual reproductive strategy of microscopic invertebrate rotifers - animals whose evolutionary history was previously thought to preclude either cooperative behavior (quorum sensing) typically associated with bacteria and hormonal regulation via progesterone typically seen in vertebrates; 5) identifying a novel aversive chemoreception pathway in predatory fish that results in rapid recognition and rejection of chemically defended foods, thereby protecting these foods (prey) from predators.
Ongoing projects include: 1) Waterborne chemical cues in the marine plankton: a systems biology approach (including metabolomics); 2) Exploration, conservation, and development of marine biodiversity in Fiji and the Solomon Islands (including drug discovery, mechanisms of action, and chemical ecology); 3) The role of sensory environment and predator chemical signal properties in determining non-consumptive effect strength in cascading interactions on oyster reefs; 4) Regulation of red tide toxicity by chemical cues from marine zooplankton; 5) Chemoreception of prey chemical defenses on tropical coral reefs.
Most biological traits have a strong genetic, or heritable, component. Understanding how genetic variation influences these phenotypes will be important for understanding common, heritable diseases like autism. However, the genetic architecture controlling most biological traits is incredibly complex – hundreds of interacting genes and variants combine in unknown ways to create phenotype. The McGrath lab is interested in using fundamental mechanistic studies in C. elegans to identify, predict, and understand how genetic variation impacts the function of the nervous system. We are studying laboratory adapted strains and harnessing directed evolution experiments to understand how genetic changes affect development, reproduction, and lifespan. We combine quantitative genetics, CRISPR/Cas9, genomics, and computational approaches to address these questions. We believe this work will lead to insights into evolution, multigenic disease, and systems biology.
Micro and nano engineering, acoustics and dynamics, micromachined ultrasonic and opto-acoustic transducers, atomic force microscopy, and medical ultrasound imaging
Dr. Degertekin's research focuses on understanding of physical phenomena in acoustics and optics, and utilizing this knowledge creatively in the form of microfabricated devices. The research interests span several fields including atomic force microscopy (AFM), micromachined opto-acoustic devices, ultrasound imaging, bioanalytical instrumentation, and optical metrology. Dr. Degertekin's research group, in collaboration with an array of collaborators, has developed innovative devices for applications such as nanoscale material characterization and fast imaging, hearing aid microphones, intravascular imaging arrays for cardiology, bioanalytical mass spectrometry, and microscale parallel interferometers for metrology.
Intercalation-mediated Nucleic Acid Assembly, The Molecular Midwife & the Origin of Life, Nucleic Acid-Cation Interactions, Understanding DNA & RNA Condensation.
The research in our laboratory is directed towards elucidating the fundamental chemical and physical principles that govern nucleic acid (RNA and DNA) assembly. We are interested in how the physical properties of nucleic acids govern biological functions in contemporary life, and how these same properties provide clues to the origin and early evolution of life. We are also applying our knowledge of nucleic acids to problems that are of current importance in medicine and biotechnology. Specific projects include investigations of: 1) the origin and evolution of RNA; 2) cation, solvent and small molecule interactions with nucleic acids; 3) nucleic acid condensation and packaging; and 4) folding and evolution of the ribosome. Our research involves the application of a wide variety of physical and chemical techniques.
A. Nanoscience: Synthesis and Study of the Properties of Nanomaterials of Different Shape: The type of electronic motion in matter determines its properties and its applications. This motion is determined by the forces acting on the electrons, which in turn, determine the space in which they are allowed to move. One expects that if we reduce the size of material to below its naturally allowed characteristic length scale, new properties should be observed which change with the size or shape of the material. These new properties are different from those of the macroscopic material, as well as of its building blocks (atoms or molecules). This phenomenon occurs on the nanometer length scale. Our group makes and studies the properties of these nanometer materials. The properties examined are:
Ultrafast electron-hole dynamics in semiconductor nanoparticles and composites
Shape-controlled synthesis and stability of metallic nanoparticles
Enhanced light absorption and scattering processes, electronic relaxation, and photothermal properties of gold and silver nanocrystals of different shapes
B. Nanotechnology: Potential Use of Nanoparticles in: a) Nanomedicine - Diagnostics and Selective Photothermal Therapy of Cancer: When gold or silver nanoparticles are conjugated to cancer antibodies or other cancer targeting molecules, the cancer cells selectively labeled with those nanoparticles and can be easily detected under a simple microscope due to their strongly enhanced light scattering properties. The fact that these nanoparticles can also absorb light strongly and rapidly convert this energy into heat allows for the selective destruction of cancer cells at laser energies not sufficient to harm surrounding healthy cells. The concept of plasmonic photothermal therapy has been demonstrated in both cell culture and in live animal models in our laboratory. In addition, we are also researching the use of plasmonic particles as selective drug delivery and imaging contrast agents. b) Nanocatalysis - Shape Dependent Catalysis: Due to their large surface to volume ratio, nanoparticles are expected to be good catalysts. Since different shapes of nanoparticles made of the same material have their surface atoms arranged differently, one expects them to have different catalytic properties. In our group, we are examining the effects of both the nanoparticle shape and the cavity size of hollow nanoparticles on the catalytic properties of transition metal nanocrystals. We are also studying the shape-stability of these nanoparticles in the harsh chemical environment of the catalytic reactions in colloidal solution. c) Plasmonics: The intense electromagnetic fields generated at the surfaces of noble metal nanoparticles – localized surface plasmons – are known to enhance radiative and non-radiative processes, as well as energy transfer processes in nearby molecules and compounds. By combining plasmonic particles with biomolecular photosystems, the rates of important chemical processes, such as retinal isomerization in photosynthetic baceriorhodopsin (bR) and its associated proton pump rate, can be tuned. This property was recently used to enhance the photocurrent from bR by a factor of 5000. Rates of radiative (emission) and non-radiative relaxation in excitonic systems, such as semiconductor quantum dots and rods, can also be dramatically enhanced by plasmon coupling interactions. LDL also studies the fundamental interactions of plasmons as they couple to one another in individual (i.e. nanoshell and nanocage) particles, as well as in groups of nanoparticles as their size, shape, distance, and orientation are varied.
Disruptive technologies enabled by nanoscale materials and devices will define our future in the same way that microtechnology has done over the past several decades. Our current research centers on the design and synthesis of novel nanomaterials for a broad range of applications, including nanomedicine, regenerative medicine, cancer theranostics, tissue engineering, controlled release, catalysis, and fuel cell technology.
We are design and synthesize/fabricate novel nanomaterials that could serve as: 1) theranostic agents for cancer and other diseases; 2) multifucntional probes for cellular tracking; 3) smart capsules for site-specific, on-demand delivery; and 4) scaffolds for the repair or regeneration of tissues.
We develop chemical and biological tools for research in a wide range of fields. Some of them are briefly described below; please see our group web page for more details.
Chemistry, biology, immunology, and evolution with viruses. The sizes and properties of virus particles put them at the interface between the worlds of chemistry and biology. We use techniques from both fields to tailor these particles for applications to cell targeting, diagnostics, vaccine development, catalysis, and materials self-assembly. This work involves combinations of small-molecule and polymer synthesis, bioconjugation, molecular biology, protein design, protein evolution, bioanalytical chemistry, enzymology, physiology, and immunology. It is an exciting training ground for modern molecular scientists and engineers.
Development of reactions for organic synthesis, chemical biology, and materials science. Molecular function is what matters most to our scientific lives, and good chemical reactions provide the means to achieve such function. We continue our efforts to develop and optimize reactions that meet the click chemistry standard for power and generality. Our current focus is on highly reliable reversible reactions, which open up new possibilities for polymer synthesis and modification, as well as for the controlled delivery of therapeutic and diagnostic agents to biological targets.
Traditional and combinatorial synthesis of biologically active compounds. We have a longstanding interest in the development of biologically active small molecules. We work closely with industrial and academic collaborators on such targets as antiviral agents, compounds to combat tobacco addiction, and treatments for inflammatory disease.
Our research focuses on LC-MS based proteomics and its biomedical applications. Novel MS based methods are being developed to characterize proteins, especially protein post-translational modifications (PTMs). MS-based large-scale analysis can systematically identify and quantify proteins and their PTMs for the different states of cells or tissues, such as cancerous samples. This may provide a better understanding of the function of proteins, the role that proteins play in physiological and pathological processes, cell signaling, cell metabolism, and the relationship between proteins and cancer.