- Postdoctoral Fellow, University of California, Berkeley, Berkeley, CA, 2001
- Ph.D., Cancer Biology, Stanford University, Stanford, CA 1996
Research Assistant Professor, Department of Biology, Rensselaer Polytechnic Institute, Troy, NY
Areas of Research
- Human Pluripotent Stem Cells (hESC, hiPSC)- Multi-lineage Studies
- Neural Stem Cells: Axonopathies, Spinal cord injury, TBI
- Human Neural Gastruloid and Organoid Models
- Neuroscience Nanotechnology and 3D Tissue Engineering
- Computational Neuroscience and Nanoscale Communication
- Disease Complexity- Aging and Ethnicity
- Cancer Biology- Cell Cycle, Mitosis, Drug discovery
- Biological Control and Self-assembling Systems-Nanomotors, MTOCs
Overview: The Paluh laboratory applies human pluripotent and neural stem cell technologies, gastruloid and organoid technologies, nanotechnology, bioengineering, computational modeling of biological networks, and biological nanomachines. Research focuses on neuropathologies, including axonopathies, spinal cord injury, traumatic brain injury, as well as in vitro formation of biological neural circuits and collaborations in software and hardware design of artificial neuromorphic synapses and machine learning applied to staging neural cancers. Additional research areas include human stem cell applications for cardiomyopathies and for bioprocessing/ biomanufacturing for diabetic cell therapy. Integrating bioinformatics and computational modeling allows us to identify contributing gene networks and cell signaling pathways from intracellular networks to cell-cell systems communication to understand normal development and disease. Recently derived xenofree human pluripotent stem cell lines from our lab include African American, Hispanic Latino and Asian ethnicities, as an expanded research and clinical resource to improve biomedical therapies by encompassing diversity. SUNY Polytechnic Institute is a bench to commercialization environment that enhances productive academic-industry partnerships and multi- academic collaborations to accelerate the pace of discovery. As a nanotechnology center we have onsite capabilities to apply custom photolithography to design high throughput microarrays, microsieves, microfluidic and patterning platforms and cell-scaffolds
Human Development and Disease
- Ethnically Diverse hiPSCs. Human induced pluripotent stem cells (iPSCs) provide an opportunity to understand key genetic and epigenetic requirements in normal tissue development and diseased states. The Paluh lab is applying ethnically diverse hiPSC lines to investigate human development, neurogenesis, cardiogenesis, aging, neurodegeneration, and cancer as well as cell therapeutics. Research in the Paluh lab derived some of the first xenofree human pluripotent stem cell lines from African American, Hispanic Latino and Asian ethnicities, as an expanded research and clinical resource to improve biomedical therapies by encompassing diversity.
- Bioengineering Niches. Directed differentiation of human stem cells, tissue and organ development and high throughput applications are benefited by collaborative efforts that combine bioengineering, biomedical, chemical and materials science engineering to develop 3D architectures that mimic the cellular environment in a spatiotemporally responsive manner. The Paluh lab is applying nanotechnology tools towards developing functionalized hydrogel scaffolds, cell patterning approaches, neural circuitry neural ribbons, and complex multi-cell type 3D tissue bioengineering.
- Human neural stem cells. Human stem cell biology offers unlimited potential for human therapies. Work in the Paluh lab is addressing neurotrauma such as spinal cord injury (SCI) and traumatic brain injury (TBI) as well as neurodegenerative axonopathies such as Alzheimer’s Disease in collaborative efforts. Generated spinal motor neurons (SMNs), interneurons and oligodendrocyte progenitors (OPCs) are used to preform neural circuitry for transplantation as neural ribbons into rat hemicontusion models of SCI. In related studies we generate gastruloids to understand requirements for neuromuscular innervation in formed elongating multi-lineage organized (EMLO) gastruloids. Recently developed EMLOCs are providing insights into development and innervation of the human embryonic heart. Cortical organoids are also being analyzed. By combining neural stem cell technologies for cortical pyramidal neurons and GABAergic interneurons we bioengineered a neural cell-cell interaction microchip, NCCIM, to evaluate neural microenvironments to benefit cell therapeutics. We apply bulk and single cell transcriptomics, bioinformatics, microscopy and biomarker analysis, patch clamp and MEA electrophysiology, evaluation of neuronal and neuromuscular synapses, calcium signaling, biomaterials and bioengineering.
Nanoscale Communication, Computational Neuroscience and Artificial Synapses
- Nanoscale Communication. Dr. Paluh participates on the IEEE Standards Association working groups, including new standards developed for defining and applying Nanoscale Communication Networks. This includes the IEEE SA Recommended Practice for Nanoscale and Molecular Communication Framework, which applies Shannon’s Rules of Communication to hybrid biological and human made systems; and IEEE SA Standard Data Model for Nanoscale Communication Systems. In addition Dr. Paluh participates in the Cell to Macroscale Working Group of the NIH IMAG MSM Interagency Modeling Analysis Group and Multiscale Modeling.
- Computational Neuroscience. The Paluh laboratory collaborates on a variety of projects to advance neuroscience through software and hardware development. Recent collaborations include Artificial Synapse pre-SyNC and SYNC software and hardware models applied to Autism synaptopathies; software models for Axonopathies, including an end to end nanocommunication model for amyloid beta oligomers and a second axonal model, DyNAMO, as one of the first axonal transport models. Additional projects include machine learning approaches to model amyloid beta oligomer (AβO) interactions with cell receptors as well as machine learning applied to brain gliomas and other neuropathologies. The longterm goal is to advance understanding of nanoscale neural mechanisms. Mathematical modeling of complex neural molecular mechanisms in the field of computational neuroscience creates opportunities for scientific discovery. These incredibly powerful tools allow nanoscale dynamic mechanisms in neurons and neural communication networks to be modeled and analyzed. Current models must often integrate quantified parameters obtained from a variety of biological systems with assumptions to test multiple scenarios and provide unique insights to guide informative experimentation. The Paluh lab collaborates with experts in telecommunication networks that provides unique perspectives to biological neural networks. This collaborative work has been presented at multiple conferences including: VLSI Design and Embedded Systems; Interagency Modeling and Analysis Group/Multiscale Modeling (IMAG/MSM); Virtual 3D Cell; Banff International Research Station (BIRF) Workshop 14W5170 Biological and Bioinspired Information Theory, and Virtual Physiological Human (VPH) meeting.
Cellular Machines: Function & NanoEngineering of the Microtubule Cytoskeleton
Overview. My lab has made fundamental contributions to understanding microtubule mechanisms. This includes novel roles for Kinesin nanomotors and insights into microtubule structure and dynamics as well as microtubule organizing center (MTOC) regulation relevant to centrosomes, spindle pole bodies and specialized γ-tubulin-nucleating complexes. A novel regulator of microtubule nucleation developed in my lab blocks the MTOC γ-TuRC, preventing mitotic spindle assembly that in vitro arrests proliferation of breast cancer lines. The upstream site of action makes this regulator of particular interest in targeting a broad range of drug resistant cancers.
- Cellular Motors and Microtubules in Nanofabrication of Microarchitectures. Cellular scaffolds and their associated proteins are ideal models of self-assembly, error correction, and environmental adaptability. These flexible principles counter typical static human designed lithography-templated platforms. Biomimicry of cellular cytoskeleton networks may help inform on how to incorporate adaptive principles into nano-microscale manufacturing including multiscale communication networks from nano-, micro- to macroscale. We are interfacing nanomotor Kinesin-like proteins (Klps), isolated MTOCs and microtubule-regulators with human-made materials to model nanoscale communication networks and engineer hybrid programmable adaptable nano-microsystems.
- Microtubule Cytoskeleton Betworks and Kinesins. The microtubule cytoskeleton and its interacting proteins and complexes drive essential processes of mitosis, neuronal function, development, and specialized functions via impacts on cell migration, ciliary function, cell signaling, cell polarity, organelle and vesicular transport, and more. At least fourteen conserved Klp families exist, but in varied combinations in eukaryotes indicating inherent flexibility in motor proteins to multitask. Kinesin roles in cytoskeleton function and self-organization go beyond the elegant kinetics of ATP hydrolysis, step movement and high-resolution co-crystals, yet the scope of kinesin-like protein (KLP) functions and mechanisms across 14 families are still vastly unexplored. Unlike dynein, KLPs are ubiquitous in eukaryotes and likely among the oldest cytoskeleton proteins in the evolution of dividing eukaryotic cells. The Paluh lab was the first to identify a conserved Kinesin-14 mechanism at the microtubule organizing center (MTOC) that regulates microtubule nucleation and spindle formation and then convert this information into a peptide reagent that blocks spindle formation and arrests growth of metastatic breast cancer lines in vitro. This was accomplished via a comprehensive set of chimeras, mutants and variants from human cross-analyzed in yeast. The Paluh lab further revealed an additional level of control by Kinesin-5 to counter Kinesin-14 at microtubule organizing centers (MTOC). The findings have implications in paclitaxel (-tubulin targeting) and monastrol (KInesin-5 targeting) treatment resistant and metastatic cancers. Work published in Nature Communications and patented. The Paluh laboratory is also exploring MTOC and Kinesin functions in neuron axonal mechanisms.
- The γ-TuRC MTOC and γ-tubulin Complexes. The Microtubule Organizing Center (MTOC) is an essential macromolecular complex and the site of microtubule growth, polarized cytoskeleton organization and dynamics as well as a scaffold and signaling hub and center for regulation, organization, axonal branching, and target of viral microcephalies. The MTOC templates α/β-tubulin dimer assembly onto a γ-tubulin ring subcomplex (γ-TuRC). Structural models and genetics arose first from yeast, but whether mechanistic conservation existed with human counterparts was unclear. The Paluh lab discovered Kinesin-14 regulation of the MTOC via γ-TuRC and demonstrated cross-species compatible roles in vivo of fission yeast and human γ-tubulin binding MTOC proteins. MTOCs underly key cellular structures that are the mitotic spindle, neural axons and dendrites, cilia and centrosome-based complexes, each providing specialized vital cellular functions. Unique reagents developed in the Paluh lab help to define at the molecular level conserved structural and functional parameters of MTOCs, focusing on regulation of the γ-tubulin complexes for biomedical or nanofabrication applications.
Selected Current and Past Professional Contributions
- Editorial Board, Scientific Reports, Nature publishing
- SUNY Polytechnic Planning and Budget Committee, co-Chair
- SUNY Polytechnic Institutional Review Board (IRB), co-Chair
- University at Albany Institutional Review Board (IRB), Chair
- Stem Cell Research Oversight (SCRO), member/former Chair
- Board of Directors, Girls Incorporated Non-Profit
- Project Lead the Way Panel ‘Nano’izing K-12’
- IEEE P1906.1 NanoCom Working Group “Recommended Practice for Nanoscale and Molecular Communication Framework”
- Faculty of 1000 Associate Faculty Reviewer, Cell Biology, Cytoskeleton
- Editorial Board, Advances in Stem Cell Discovery
- NSF MRI Panel, Division of Biological Infrastructure
- Mentor for 2013 Goldwater Scholar undergraduate awardee
- Nina Notman (Dec 2014) Let Molecules Do the Talking, Chemistry World. http://www.rsc.org/chemistryworld/2014/12/let-molecules-do-talking
- Paula Monaco (Sept 2013) Under the Microscope, Capital Magazine, Albany, NY
- Paul Grondahl (Mar 2013) Innovators Series: Ready to Unlock Stem Cell Mysteries, Times Union, Albany, NY
Recent Publications and Book Chapters
- Z.T. Olmsted and J.L. Paluh (2021) Stem cell neurodevelopmental solutions for restorative treatments of the human trunk and spine. Frontiers in Cellular Neuroscience. In press
- Z.T. Olmsted and J.L. Paluh (2021) Co-development of central and peripheral neurons with endoderm in elongating multi-lineage organized (EMLO) gastruloids. Nature Communication. In press
- Rounak, Paluh, Mukherjee (2021) Pre-SYNC: Hardware realization of the pre-synaptic region of a biologically extensive neural circuitry. 34th International Conference on VLSI Design & 20th International Conference on Embedded Systems.
- Rounak, Paluh, Mukherjee (2021) SyNC, a computationally extensive and realistic neural net to identify relative impacts of synaptopathy mechanisms on glutamatergic neurons and their networks in Autism and complex neurological disorders. Frontiers in Cellular Neuroscience. In review
- Z.T. Olmsted and J.L. Paluh (2021) Transplantable human motor networks as a neuron-directed strategy for spinal cord injury. iScience. In review.
- Z.T. Olmsted, C. Stigliano, B. Marzullo, J. Cibelli, P.J. Horner, J.L. Paluh (2021) Mature human iPS- and NMP- derived motor neurons thrive without neuroprotection in the spinal contusion cavity. Stem Cell Reports. In review.
- S. Chandra, J.L. Paluh, R. Chatterjee, A. Mukherjee and S. Pal (2021) A dynamic nanoscale axonal microtubule organization, DyNAMO, model reveals interplay of kinesin with staggered microtubule bundles along the axon length. Manuscript in preparation.
- A. Banerjee, J. L. Paluh, A. Mukherjee, K. G. Kumar, A. Ghosh, M. K. Naskar (2017) Modeling the neuron as a nano communication system to identify spatiotemporal molecular events in neurodegenerative disease. International J Nanomedicine, 13:3105-3128. doi: 10.2147/IJN.S152664. PMID: 29872297
- P. Zhao, J. George, B. Li, N. Amini, J. Paluh, J. Wang (2017) Clickable multi-functional dumbbell particles for in situ multiplex single-cell cytokine detection. ACS Applied Material Interfaces. 9:32482-32488. PMID: 28884571.
- M.L. Tomov, Z.T. Olmsted, H. Dogan, E. Gongorurler, M. Tsompana, H.H. Otu, M. Buck, E-A. Chang, J. Cibelli, and J.L. Paluh (2016). Distinct and shared determinants of cardiomyocyte contractility in multi-lineage competent ethnically diverse human iPSCs. Sci Reports 6:37637. Doi: 10.1038/srep37637. PMID: 27917881
- M.L. Tomov, M.Tsompana, Z.T. Olmsted, M. Buck, and J.L. Paluh (2016). Human Embryoid Body transcriptomes reveal maturation differences influenced by size and formation in custom microarrays. J Nanosci Nanotech 16:8978-8988. Special Issue Nanotechnology in Stem Cell Research. Doi: 10.1166/jnn.2016.12734
- J.Wang, B.Egnot, J.L.Paluh (2016) Cell competition and cooperation in tissue development. J Tissue Sci Eng. 7:131. Doi: 10.4172/2157-7552.1000131
- Paluh JL (2016) Epigenetics, Ethnicity, Bioinformatics and Nanotechnology Opening Frontiers in Cardiac Medicine. International Journal of Stem Cell Research and Therapy 3:027. ISBN: 2469-570X
- E-A Chang, M.L. Tomov, S.T. Suhr, J. Luo, Z.T. Olmsted , J.L. Paluh, and J. Cibelli (2015). Derivation of ethnically diverse human pluripotent stem cell lines. Scientific Reports.5:15234. Doi: 10.1038/srep15234
- S.F. Bush, J.L. Paluh, G. Piro, V. Rao, V. Prasad, A. Eckford, et al. (2015) P1906.1TM-2015 Recommended Practice for Nanoscale and Molecular Communication Framework. IEEE Standards Association Active Standard. ISBN: 978-1-5044-01-1-2
- S.F. Bush, J.L. Paluh, G. Piro, V. Rao, V. Prasad, and A. Eckford (2015) Defining Communication at the Bottom. IEEE Journal series on Selected Areas of Communication (JSAC): Transactions in Molecular, Biological and Multi-Scale Communications. DOI: 10.1109/TMBMC.2015.2465513
- M.L. Tomov, Z.T. Olmsted, and J.L. Paluh (2015) The human embryoid body cystic core exhibits architectural complexity revealed by use of high throughput polymer microarrays. Macromolecular Biosciences. 2015, DOI: 10.1002/mabi.201500051. PMID: 25810210.
- Z.T. Olmsted, A. Colliver, and J.L. Paluh (2015) The Kinesin-tubulin complex: Mechanistic considerations in structure and function. Cell Health and Cytoskeleton, Volume 2015:7, 83-97. DOI http://dx.doi.org/10.2147/CHC.S75310
- Z.T. Olmsted, A. Colliver, T.D. Riehlman, and J.L. Paluh (2014) Kinesin-14 and kinesin-5 antagonistically regulate microtubule nucleation γ-TuRC in yeast and human cells. Nature Communications 5:5339. PMID:25348260
- T.D. Riehlman, Z.T. Olmsted, C.N. Branca, A. Winnie, L. Seo, L.O. Cruz, and J.L. Paluh (2013) Functional replacement of fission yeast γ-tubulin small complex proteins Alp4 and Alp6 by human GCP2 and GCP3. J Cell Sci. 126: 4406-4413. PMID: 23886939
- Z.T. Olmsted, T.D. Riehlman, C.N. Branca, A. Colliver, A. Winnie and J.L. Paluh (2013) Kinesin-14 Pkl1 targets γ-tubulin for release from the γ-tubulin ring complex (γ-TuRC). Cell Cycle 12(5): 842-848. PMID: 23388459
- L. Gasimli, H.E. Stansfield, A.V. Nairn, H. Liu, J.L. Paluh, B. Yang, J.S. Dordick, K.W. Moreman, and R. J. Linhardt (2013) Structural remodeling of proteoglycans on retinoic acid-induced differentiation of NCCIT cells. Glyconjugate J. 30: 497-510. PMID: 23053635.
- T.D. Riehlman, Z.T. Olmsted, and J.L. Paluh (2012) Nanomachines: Molecular Motors, Chapter in Nanotechnology Handbook, CRC Press/Taylor and Francis Group. ISBN:9781439838693
- J.L. Paluh, J.L. (2011) Towards nanorobotics, nanonetworks, and self-assembling and regulating machines. Nanotechnology Now. http://www.nanotech-now.com/columns/?article=507
- J.L. Paluh, G. Dai, and D.B. Chrisey (2011) In search of the Holy Grail: Engineering the stem cell niche. European Pharmaceutical Review. 16(2): 28-33
- B. Riggs, J.L. Paluh, G. Plopper, and D.B. Chrissy (2011) Impedence Spectroscopy for Characterization of Biological Function, Chapter 12 in NanoCellBiology: Multimodal Imaging In Biology and Medicine, Pan Sanford Publishing Pte. Ltd. ISBN: 9789814411790
- D.R. Simeonov, K. Kenny, A. Moyer, L. Seo, J. Allen, and J.L. Paluh (2009) Distinct Kinesin-14 mitotic mechanisms in spindle bipolarity. Cell Cycle 8(21): 3571-3583. PMID:19838064 * featured in News and Views, 8(21): 3452-3454. PMID:19855184
- J.L. Paluh (2008) Sentinels of DNA integrity in stem cells. Cell Cycle 7(18): 2779-2780. DOI: 10.4161/cc.7.18.6890
- J.L. Paluh (2008) Kinesin-14 leaps to pole position in bipolar spindle assembly. Chinese Journal of Cancer, 27(9): 1-5. PMID:18799042
- A.S. Rodriguez, J. Batac, A.N. Killilea, J. Filopei, D.R. Simeonov, I. Lin, and J.L. Paluh (2008) Protein complexes at the microtubule organizing center regulate bipolar spindle assembly. Cell Cycle. 7(9): 1246-1253. PMID:18418055
- C.L. Mayer, J. Filopei, J. Batac, L. Alford, and J.L. Paluh (2006) An extended signaling pathway for Mad2p in anaphase includes microtubule organizing center proteins and multiple motor-dependent transitions. Cell Cycle. 5: 1456-1463. PMID:16855399
- J.L. Paluh, A.N. Killilea, W. Detrich III, and K. Downing (2004) Meiosis-specific failure of cell cycle progression in fission yeast by mutation of a conserved β-tubulin residue. Mol. Biol Cell. 15: 1160-1171. PMID:14657251
- J.L. Paluh, E. Nogales, B.R. Oakley, K. McDonald, A.L. Pidoux, and W.Z. Cande (2000) A mutation in γ-tubulin alters microtubule dynamics and organization and is synthetically lethal with the Klp Pkl1p. Mol. Biol. Cell 11: 1225-1239. PMID:10749926
- J.L. Paluh and Z.T. Olmsted. Microtubule Organizing Center (MTOC) Inactivating Peptides. U.S. Patent 9567380
International Presentations of Research
- Virtual Physiological Human (VPH), Computational Neuroscience of Axonopathies, 2018
- Biophysical Society Thematic Meeting: Engineering Approaches to Biomolecular Motors from in vitro to in vivo. Canada, June 2016.
- Workshop 14w5170: Biological and Bio-Inspired Information Theory. Banff International Research Station for Mathematical Innovation and Discovery (BIRS), Canada, Oct 2014.
- EMBO Conference on Centrosomes and Spindle Pole Bodies, Heidelberg, Germany, Sept 2008
- EMBO Workshop on Centrosomes and Spindle Pole Bodies, Heidelberg, Germany, Sept 2005
- Paterson Institute for Cancer Research, Manchester, United Kingdom, July 2004
- European Pombe Meeting, Lausanne, Switzerland, June 2003
- EMBO/EMBL Conference on Centrosomes and Spindle Pole Bodies, Heidelberg, Germany, Sept 2002
- Second International Fission Yeast Meeting, Kyoto, March 2002
- EMBO Workshop on Centromeres, Kinetochores and Spindle Function, Heidelberg, Germany, October 2000
- First International Fission Yeast Meeting, Edinburgh, Scotland, September 1999
National Presentations of Research
- Society for Neuroscience, minisymposium. SCI neural ribbon therapy. Chicago, IL, August 2017.
- SUNY Academic Industry Roundtable (AIR), Precision Medicine in Oncology. NYC, NY January 2016
- RPI Bioengineering and Stem Cell Research Conference, June 2015
- NIH NIA, National Council on Aging, Task Force on Minorities and Health Disparities Research, May 2015
- Western New York Stem Cell Conference (WNYSTEM), SUNY Buffalo, NY June 2015.
- Society of Biological Engineers and International Society of Stem Cell Research (SBE-ISSCR), 4th International Conference on Stem Cell Engineering. Coronado, CA, Febr 2014
- Capital Region Cancer Research Group, Albany, NY, June 2014
- Spinal Cord Society Capital District Chapter, 29th Annual Research Benefit, April 2013
- NYSTEM Collaboration and Renewal Annual Conference. New York, NY May, 2013
- Capital Region Cancer Research New Frontiers Symposium, Albany, NY Nov 2012.
- North American Regional Pombe Meeting, University of California, Los Angeles, CA, June 2008
- American Cancer Society, Relay for Life, Troy, NY, May 2008
- Sanford/Burnham Medical Research Institute, Stem Cells and Regenerative Biology, La Jolla, CA, July 2006
- Buck Institute for Research on Aging, Novato, CA, July 2006
- Second East Coast Regional Fission Yeast Meeting, Miami, FL, November 2005
- Department of Cell Biology, Emory University School of Medicine, Atlanta, GA. May 2005
- Third International Fission Yeast Meeting, San Diego, CA, August 2004
- Annual Meeting American Society of Cell Biology, Minisymposium: Spindles and Spindle Poles, Washington D.C., Dec 1999
Selected Educational Presentations
- Project Lead the Way Innovation Summit, Panelist ‘Nano’izing K-12’ Washington, D.C. Oct 2010.
- NEATEC, Northeastern Advanced Technological Innovation Center, ‘Preparing the Technology Workforce’. Hudson Valley Community College, Rensselaer, Nov 2011.
- ESATCYB, Empire State Association of Two-Year College Biologists, Annual Conference, ‘Nanotechnology in Research and Education’, Fulton-Montgomery Community College, Johnstown, NY, April 2012.
- SUNYIT Nanotechnology Forum, “Nanotech 101” Utica, NY, May 2012.
- The OASIS Organization for healthy ageing, ‘Nanotechnology and Stem Cells’, Albany, NY, Nov 2011.