Faculty and Research

Focus Areas of PBSB faculty:

  • Biophysical and Physiological Mechanisms of Membranes and Membrane  Proteins: Work in the labs of Drs. Anderson, Boudker, Christini, Palmer, and H. Weinstein has uncovered remarkable molecular properties of channels and receptors that make possible cell function and intercellular communication in the brain, and throughout the body. The discrete mechanisms of these complex molecules were revealed from creative experimental designs, as well as computational modeling and simulation. In parallel, the discovery of some previously unknown genes and their function has enabled the laboratories of Drs. Huang and Weinstein to outline the signal transduction mechanisms that connect the membrane protein signals to gene expression and regulation. All these insights enable as well the development of novel therapies and the design of targeted drugs.

  • Quantitative and Integrative Systems Biology: With quantitative measurements of physiological processes, mathematical modeling, computational simulation, and bioinformatics, the laboratories of Drs. Aksay, Clancy, Christini, Gardner, Leibler, Nirenberg, Victor, A.M. Weinstein, and H. Weinstein have represented the components and calculated the parameters of fundamental mechanisms in neurophysiology and in the function of organs such as the heart. The approaches include construction and interpretation of gene or cell signaling networks for which a variety of questions are answered, such as the robustness and sensitivity of networks with respect to biochemical modifications of their components, the resistance of genetic networks to molecular noise, such as the noise connected with fluctuations in the number of different components, and the precision and establishment of proportions (scaling) in spatial pattern formation. The formal and quantitative models can create a new perspective on how the cellular and network properties of individual neurons, and the information they convey, give rise to the complex behavior of the brain. The mathematical models are able to integrate experimental information from basic and clinical studies to reveal the most fundamental underpinning of complex physiological mechanisms, and the mode of perturbation by disease or genetic mutations.  For example, mathematical modeling of solute and water transport across the renal epithelia are developed to produce a mathematical model of the mammalian distal nephron in order to assess the extent to which known defects can account for observed solute excretion patterns. Conversely, simulations of clinical tests of distal nephron function can be used to evaluate their accuracy in defining a specific transport defect. Similarly, modeling of ion channels in heart cells where molecular defects disrupt the delicate balance of dynamic interactions between the ion channels and the cellular environment, results in simulations that reveal how the resulting altered cell function manifests itself as cardiac arrhythmia.

  • Organogenesis and Physiological Genomics:  To answer the key questions about the development of the complex functions in specialized cells of tissues and organs, the laboratories of Drs. Basson, Herzlinger and Coonrod identify both the genes that regulate differentiation, and the nature of the inductive signal that triggers multipotent organogenic progenitors to differentiate. For example, molecular genetic techniques were applied to identify novel genes that regulate cardiac differentiation and morphogenesis, in order to understand a number of congenital and inherited disorders of human cardiac growth and development. Similarly, a single gene product was shown to trigger embryonic renal cell differentiation. The life span of animals is also genetically controlled, and the rate of cellular aging can be regulated by genes that directly affect intracellular mechanisms for protection, turnover, and repair of macromolecules and cell membranes. The lab of Dr. Huang has developed a genetic screen for gene mutations that extend life-span in Drosophila, and has isolated a mutant methuselah (mth) that displays increased average life-span and enhanced resistance to various forms of stress. The mth gene encodes a membrane protein (G protein-coupled receptor) that signals to biochemical mechanisms regulating the aging process.

  • Aspects of Biomedical Imaging and Bioengineering: Faculty members with laboratories at the Hospital for Special Surgery (Drs. Boskey, Torzilli) and in the Imaging Center (Ballon, Wang) complement the quantitative research aspects with perspectives on physiological processes in tissue engineering, and the biophysics of biomedical imaging. The research directions include quantitative aspects of the physiology of biomineralization, analyzed with biophysical methods from the structure of mineral and matrix in health and disease, and the engineering of soft tissues. Such approaches take advantage of and are often supported by development and application of novel techniques for imaging tissues and mechanisms, e.g., of malignancies of the bone marrow, breast and other organs. New methods are being developed to assess properties and understand mechanisms of drug delivery, so as to provide insights needed for new therapies and tissue engineered products.