Bio

Academic Appointments


Honors & Awards


  • RUNN Resident Research Award, Congress of Neurological Surgeons (CNS) (2009)
  • Neurosurgery Research and Education Foundation (NREF) Fellowship, American Association of Neurological Surgeons (AANS) (2008)
  • Glasgow-Rubin Achievement Award, Columbia University College of Physicians and Surgeons (2004)
  • Seymour L Kaplan Memorial Scholarship, Columbia University College of Physicians and Surgeons (2003)
  • Alpha Omega Alpha, Columbia University College of Physicians and Surgeons (2003)
  • University of Toronto Open Fellowship, University of Toronto (1992)
  • Life Sciences Summer Studentship, University of Toronto (1991)
  • Trinity College Scholarship, University of Toronto (1990)

Professional Education


  • Fellowship, Cleveland Clinic, Complex Spine (2012)
  • Residency, Brigham and Women's Hospital/Children's Hospital Boston/Harvard Medical School, Neurosurgery (2011)
  • MD, Columbia University (2004)
  • PhD, Cold Spring Harbor Laboratory/SUNY Stony Brook, Genetics (2000)
  • MSc, University of Toronto, Anatomy and Cell Biology (1994)
  • BSc, University of Toronto, Physiology (1991)

Research & Scholarship

Current Research and Scholarly Interests


The long-term goal of the research in my lab is the repair of damaged corticospinal circuitry. Attempts at therapeutic regeneration are limited both by the current understanding of the mechanisms that underlie the sequential generation and development of corticospinal motor neurons (CSMN) and by the current understanding of the events occurring within CSMN in the setting of spinal cord injury. A thorough understanding of the molecular controls over CSMN development might enable enhancement of corticospinal regeneration. MicroRNAs are small, non-coding RNAs that have recently been identified to regulate the expression of entire “suites” of genes during the development of species as diverse as plants, worms, and humans. The work in my lab seeks to identify microRNA controls over the CSMN development and over CSMN response to spinal cord injury.

microRNA CONTROLS OVER CORTICOSPINAL MOTOR NEURON DEVELOPMENT: In collaboration with my postdoctoral mentor, Dr. Jeffrey Macklis, I have characterized differential miRNA expression in CSMN vs. callosal projection neurons (CPN) during their early differentiation. We identified a number of candidate microRNAs that may play roles in shaping CSMN and CPN development. In my lab, we are testing the ability of these microRNAs to direct CSMN development. We are also identifying targets of differentially regulated miRNAs in CSMN.

microRNA CONTROLS OVER CSMN RESPONSE TO SPINAL CORD INJURY: This work seeks to identify and investigate microRNAs differentially expressed in CSMN in the setting of acute spinal cord injury. In addition, building upon candidate microRNAs identified as controls over CSMN development, my group will also specifically investigate their roles in the response of CSMN to acute spinal cord injury, and their possible roles in recovery.

I encourage medical and undergraduate students to contact me if they are interested in being part of my lab. This is an opportunity to participate from the start in some exciting basic and translational research in a field still in its infancy. For undergraduates considering medical school, medical students considering neurosurgery, or lab members simply wishing to understand the clinical motivation of my research, there may also be opportunities for members of my group to shadow me in my clinical work at the Palo Alto VA.

Publications

Journal Articles


  • A microfluidic device to investigate axon targeting by limited numbers of purified cortical projection neuron subtypes INTEGRATIVE BIOLOGY Tharin, S., Kothapalli, C. R., Ozdinler, P. H., Pasquina, L., Chung, S., Varner, J., Devalence, S., Kamm, R., Macklis, J. D. 2012; 4 (11): 1398-1405

    Abstract

    While much is known about general controls over axon guidance of broad classes of projection neurons (those with long-distance axonal connections), molecular controls over specific axon targeting by distinct neuron subtypes are poorly understood. Corticospinal motor neurons (CSMN) are prototypical and clinically important cerebral cortex projection neurons; they are the brain neurons that degenerate in amyotrophic lateral sclerosis (ALS) and related motor neuron diseases, and their injury is central to the loss of motor function in spinal cord injury. Primary culture of purified immature murine CSMN has been recently established, using either fluorescence-activated cell sorting (FACS) or immunopanning, enabling a previously unattainable level of subtype-specific investigation, but the resulting number of CSMN is quite limiting for standard approaches to study axon guidance. We developed a microfluidic system specifically designed to investigate axon targeting of limited numbers of purified CSMN and other projection neurons in culture. The system contains two chambers for culturing target tissue explants, allowing for biologically revealing axonal growth "choice" experiments. This device will be uniquely enabling for investigation of controls over axon growth and neuronal survival of many types of neurons, particularly those available only in limited numbers.

    View details for DOI 10.1039/c2ib20019h

    View details for Web of Science ID 000311069200008

    View details for PubMedID 23034677

  • Cervical spine arthroplasty: fact or fiction: the absence of need for arthroplasty. Clinical neurosurgery Tharin, S., Benzel, E. C. 2012; 59: 82-90

    View details for PubMedID 22960518

  • Functional brain mapping and its applications to neurosurgery NEUROSURGERY Tharin, S., Golby, A. 2007; 60 (4): 185-201

    Abstract

    Functional brain mapping may be useful for both preoperative planning and intraoperative neurosurgical decision making. "Gold standard" functional studies such as direct electrical stimulation and recording are complemented by newer, less invasive techniques such as functional magnetic resonance imaging. Less invasive techniques allow more areas of the brain to be mapped in more subjects (including healthy subjects) more often (including pre- and postoperatively). Expansion of the armamentarium of tools allows convergent evidence from multiple brain mapping techniques to bear on pre- and intraoperative decision making. Functional imaging techniques are used to map motor, sensory, language, and memory areas in neurosurgical patients with conditions as diverse as brain tumors, vascular lesions, and epilepsy. In the future, coregistration of high resolution anatomic and physiological data from multiple complementary sources will be used to plan more neurosurgical procedures, including minimally invasive procedures. Along the way, new insights on fundamental processes such as the biology of tumors and brain plasticity are likely to be revealed.

    View details for DOI 10.1227/01.0000255386.95464.52

    View details for Web of Science ID 000245607100001

    View details for PubMedID 17415154

  • The short coiled-coil domain-containing protein UNC-69 cooperates with UNC-76 to regulate axonal outgrowth and normal presynaptic organization in Caenorhabditis elegans. Journal of biology Su, C., Tharin, S., Jin, Y., Wightman, B., Spector, M., Meili, D., Tsung, N., Rhiner, C., Bourikas, D., Stoeckli, E., Garriga, G., Horvitz, H. R., Hengartner, M. O. 2006; 5 (4): 9-?

    Abstract

    The nematode Caenorhabditis elegans has been used extensively to identify the genetic requirements for proper nervous system development and function. Key to this process is the direction of vesicles to the growing axons and dendrites, which is required for growth-cone extension and synapse formation in the developing neurons. The contribution and mechanism of membrane traffic in neuronal development are not fully understood, however.We show that the C. elegans gene unc-69 is required for axon outgrowth, guidance, fasciculation and normal presynaptic organization. We identify UNC-69 as an evolutionarily conserved 108-amino-acid protein with a short coiled-coil domain. UNC-69 interacts physically with UNC-76, mutations in which produce similar defects to loss of unc-69 function. In addition, a weak reduction-of-function allele, unc-69(ju69), preferentially causes mislocalization of the synaptic vesicle marker synaptobrevin. UNC-69 and UNC-76 colocalize as puncta in neuronal processes and cooperate to regulate axon extension and synapse formation. The chicken UNC-69 homolog is highly expressed in the developing central nervous system, and its inactivation by RNA interference leads to axon guidance defects.We have identified a novel protein complex, composed of UNC-69 and UNC-76, which promotes axonal growth and normal presynaptic organization in C. elegans. As both proteins are conserved through evolution, we suggest that the mammalian homologs of UNC-69 and UNC-76 (SCOCO and FEZ, respectively) may function similarly.

    View details for PubMedID 16725058

  • Regulation of calcium binding proteins calreticulin and calsequestrin during differentiation in the myogenic cell line L6 JOURNAL OF CELLULAR PHYSIOLOGY THARIN, S., Hamel, P. A., Conway, E. M., Michalak, M., Opas, M. 1996; 166 (3): 547-560

    Abstract

    In this report we defined the structural and temporal limits within which calreticulin and calsequestrin participate in the muscle cell phenotype, in the L6 model myogenic system. Calreticulin and calsequestrin are two Ca2+ binding proteins thought to participate in intracellular Ca2+ homeostasis. We show that calsequestrin protein and mRNA were expressed when L6 cells were induced to differentiate, during which time the level of expression of calreticulin protein did not change appreciably. Calreticulin mRNA levels, however, were constant throughout L6 cell differentiation except for slight decline in the mRNA levels at the very late stages of L6 differentiation (day 11-12). We also show that the two Ca2+ binding proteins are coexpressed in differentiated L6 cells. Based on its mobility in SDS-PAGE, L6 rat skeletal muscle cells in culture expressed cardiac isoform of calsequestrin. In the mature rat skeletal muscle, calreticulin and calsequestrin were localized to sarcoplasmic reticulum (SR). Calreticulun, but not calsequestrin, staining was also observed in the perinuclear region. These data suggest that expression of calreticulin and calsequestrin may be under different control during myogenesis in rat L6 cells in culture.

    View details for Web of Science ID A1996TX60300009

    View details for PubMedID 8600158

  • WIDESPREAD TISSUE DISTRIBUTION OF RABBIT CALRETICULIN, A NONMUSCLE FUNCTIONAL ANALOG OF CALSEQUESTRIN CELL AND TISSUE RESEARCH THARIN, S., Dziak, E., Michalak, M., Opas, M. 1992; 269 (1): 29-37

    Abstract

    Calreticulin was identified in a variety of rabbit tissues by Western blot analysis. Indirect immunofluorescence studies on cultured cells or frozen sections from the corresponding tissues revealed that the protein was distributed to the endoplasmic reticulum or sarcoplasmic reticulum. Calreticulin was found to be an abundant calcium-binding protein in non-muscle and smooth muscle cells and a constituent calcium-binding protein in cardiac and skeletal muscle. From the immunoblot data, calreticulin may exist as an isoform in rabbit neural retina. The present study establishes the ubiquity of calreticulin in intracellular calcium binding.

    View details for Web of Science ID A1992JB37000004

    View details for PubMedID 1423482

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