Research Webpage

https://www.sunypoly.edu/research/paluh-research-group.html

Degrees

• Postdoctoral Fellow, University of California, Berkeley, Berkeley, CA, 2001
• Ph.D., Cancer Biology, Stanford University, Stanford, CA 1996

Experience

• Research Assistant Professor, Department of Biology, Rensselaer Polytechnic Institute, Troy, NY

Areas of Research

• Ethnically Diverse Patient Specific Induced Pluripotent Cells (hiPSCs)
• Neurodegenerative Trauma- Spinal Cord Injury (SCI), Traumatic Brain Injury (TBI)
• Neurodegeneration- Aging, Axonopathies, Synaptopathies
• Neural Circuitry via Human Gastruloid and Organoid Models
• Neuroscience Nanotechnology and 3D Tissue Bioengineering
• Computational Neuroscience and AI Machine Learning
• Cancer- Imaging and Mechanisms
• M.D. Ph.D. research training

Overview: My primary research goals and collaborations are on applying neurotechnologies to understanding neurodevelopment and repair of human central and peripheral nervous systems (CNS and PNS) for therapeutic applications. Our studies investigate normal neurodevelopment and neuropathologies that include traumatic injuries to neural circuits and tissues in SCI and TBI and neurodegenerative diseases often have a basis in neuron mechanisms that are central to neural communication referred to as axonopathies and synaptopathies. These have broader impacts including complex disorders such as Autism Spectrum Disorder (ASD).  The nanoscale dimensions of neurons means that mathematical models play a critical role in understanding neuronal signaling dynamics underlying complex diseases and fundamental to treatments. In collaborative work my laboratory is advancing computational and artificial intelligence and machine learning tools to address complex synaptic diseases in humans, such as ASD, and applying these tools as well to biomedical imaging of brain pathologies. Additional collaborative research includes scaling of biomanufacturing for patient specific therapeutics. Our studies use hiPSC lines from fibroblasts of ethnically diverse self-designated African American, Hispanic Latino, Asian and Caucasian individuals. We are always happy to collaborate on exciting new research to advance our understanding and treatments for CNS and PNS human diseases.  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 with computer chip technologies.

Human Development and Disease

• Ethnically Diverse hiPSCs. Future biomedical treatments need to reflect a diverse population that enables patient specific treatments to be optimized. 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 multidisciplinary efforts that combine bioengineering, chemical and materials science engineering to biomedical applications. This includes development of 3D architectures that mimic the cellular environment in a spatiotemporally responsive manner.  In spinal cord injury research the Paluh laboratory is generating transplantable pre-formed neuronal circuitry of region specific spinal motor neurons and neural cells to benefit advanced recovery from injury and establish an in vitro model for analysis and optimization of neural circuitry interfaces.
• Human gastruloids and organoids. Human stem cell gastruloid technology enables us to understand requirements for neuromuscular innervation of organs and tissues by the CNS and PNS.  Early neural crest cells (NCCs) are fundamental to organizing innervation. We recently developed novel technology that for the first time includes both CNS and PNS neurons in development of the early human gut and innervation of the human heart.   In contrast organoids offer solutions to modeling region specific domains in the CNS, such as cortical or hippocampal, as well as interactions of excitatory and inhibitory neurons, such as cortical pyramidal neurons and GABAergic interneurons. These technologies can also interface with biosensors such as in a neural cell-cell interaction microchip, NCCIM, to evaluate cytokine signaling of tissue context. We apply also a suite of tools that are 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 was fundamental in helping to develop the IEEE Standards Association (SA) Recommended Practice for Nanoscale and Molecular Communication Framework, which applies Shannon’s Rules of Communication to hybrid biological and human made systems; and the following IEEE SA Standard Data Model for Nanoscale Communication Systems. Dr. Paluh also participates in the Cell to Macroscale Working Group of the NIH IMAG MSM Interagency Modeling Analysis Group and Multiscale Modeling and other team efforts to advance frameworks.
• Modeling Axonopathies. Mathematical modeling of complex neural molecular mechanisms creates opportunities for scientific discovery. DyNAMO, is one of the first axonal transport models available that takes into account the complex 3D microstructure of the axonal cytoskeleton.  It stems from initial first of its kind multi-compartment analysis of molecular mechanisms in neurons in Alzheimer’s Disease.  Here we modeled amyloid beta oligomer (AβO) interactions with neuron cell surface ion channels and receptors, pore-forming capability of AβOs, internal release of calcium stores, and impact on axonal transport.  These incredibly powerful computational tools reveal nanoscale dynamics and interactions and integrate quantified parameters where available. DyNAMO allows scenario testing of new models for molecular insights to guide future informative experimentation.
• Artificial Synapses and Neural Networks: The Paluh laboratory is collaborating to develop Artificial Synapse pre-SyNC and SYNC software and hardware combined models for understanding complex neuropathologies such as Autism Spectrum Disorders that have underlying synaptic dysfunctions.  This work is also applicable to broader neural circuitry analysis in a variety of human cognitive, psychological and trauma disorders. This work is being expanded to allow a searchable platform to optimize selection of drugs treatments of ASD based on underlying mechanisms of pre- and post-synaptic dysfunctions. Software and Hardware co-development maximizes analysis with portability.
• Dissemination of findings: 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) meetings.

Cellular Machines: Function & NanoEngineering of the Microtubule Cytoskeleton

• Cancer Therapeutics.  Mitotic mechanisms are highly conserved throughout the origin of eukaryotes. This means that fundamental mechanisms exist in addition to species-specific specializations.  By analysis of fundamental mitotic mechanisms in fission yeast we generated novel reagents for arrest of cell division that are peptide regulators and demonstrated their effectiveness in tissue culture models of metastatic breast cancer lines. The peptides target the ability of the cell to generate spindle microtubules and so it acts upstream of current therapeutics that bind to microtubules or motor proteins of already formed spindles. The technology is described in Nature Communications and is expected to be useful to generate future therapeutics to be used alone or in temporally combined therapies  (Patent no: 9,567,380).
• The γ-TuRC MTOC in cell division and neuronal function. 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 microtubule formation as a site of α/β-tubulin dimer assembly onto a γ-tubulin ring subcomplex (γ-TuRC). Structural models and genetics arose first from yeast and the Paluh laboratory demonstrated functional conservation cross-species between fission yeast and humans.  MTOCs underlie key cellular structures that are the mitotic spindle, neural axons and dendrites, cilia and centrosome-based complexes, each providing specialized vital cellular functions. The Paluh laboratory has developed unique reagents for continued analysis of MTOC functions in neurons.
• Molecular Motors. Kinesin roles in microtubule 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 laboratory has focused on Kinesin-14 and Kinesin-5 motors in mitotic mechanisms leading to potential novel cancer therapeutics and is now focusing on these roles in neuron axonal mechanisms.  
• Biomimicry of cytoskeleton networks. The Paluh laboratory is interested in incorporating the adaptive dynamic capabilities of microtubule cytoskeleton networks into novel nano-microscale manufacturing platforms, such as 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.

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

Interviews

1. Nina Notman (Dec 2014) Let Molecules Do the Talking, Chemistry World. http://www.rsc.org/chemistryworld/2014/12/let-molecules-do-talking
2. Paula Monaco (Sept 2013) Under the Microscope, Capital Magazine, Albany, NY
3. Paul Grondahl (Mar 2013) Innovators Series: Ready to Unlock Stem Cell Mysteries, Times Union, Albany, NY

Recent Publications and Book Chapters

1. Z.T. Olmsted and J.L. Paluh (2021) A gastruloid model for intrinsic neural integration of the chambered human heart. In preparation.  
2. 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. In preparation.
3. T. Naidu, R. Chatterjee, S. Biswas, A. Chatterjee, A. Raha, A. Mukherjee, and J.L. Paluh (2021) An energy efficient CNN-based hardware accelerator for discernable classification of brain neuropathologies using MRI. 35th International Conference on VLSI Design & 20th International Conference on Embedded Systems.
4. Z.T. Olmsted, C. Stigliano, B. Marzullo, A. Scimemi, J. Cibelli, P. Horner, and J.L. Paluh (2020) Fully characterized mature human iPS- and NMP- derived motor neurons thrive without neuroprotection in the spinal contusion cavity. Frontiers Cellular Neuroscience. In revision.
5. R. Chatterjee, J.L. Paluh, S. Chowdhury, S. Mondal, A. Raha, and A. 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. 15:674030. doi: 10.3389/fncel.2021.674030
6. R. Chatterjee, S. Chowdhury, S. Mondal, A. Raha, J.L. Paluh, and A. 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.
7. Z.T. Olmsted, C. Stigliano, A. Scimemi, T. Wolfe, J. Cibelli, P.J. Horner, and J.L. Paluh (2021) Transplantable human motor networks as a neuron-directed strategy for spinal cord injury. iScience. 24:102827. doi: 10.1016/j.isci.2021.102827
8. 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. 15:667590. doi: 10.3389/fncel.2021.667590
9. Z.T. Olmsted and J.L. Paluh (2021) Co-development of central and peripheral neurons with trunk mesendoderm in human elongating multi-lineage organized gastruloids. Nature Communications 12:3020. doi: 10.1038/s41467-021-23294-7
10. Z.T. Olmsted, C. Stigliano, A. Badri, F. Zhang, A. Williams, M.A.G. Koffas, Y. Xie, R. Linhardt, J. Cibelli, P. Horner and J.L. Paluh (2020) Fabrication of homotypic neural ribbons as a multiplex platform optimized for spinal cord delivery. Scientific Reports. 10:12939. doi: 10.1038/s41598-020-69274-7
11. M.A.A. Abdullah, N. Amini, L. Yang, J.L. Paluh and J. Wang (2020) Multiplexed analysis of neural cytokines signaling by a novel neural cell-cell interaction microchip. Lab Chip. 20:3980-3995. doi: 10.1039/d0lc00401d
12. N. Amini, J.L. Paluh, Y. Xie, V. Saxena, and S.T. Sharfstein (2020) Insulin production from hiPSC-derived pancreatic cells in a novel wicking matrix bioreactor. Biotechnology and Bioengineering. doi.org/10.1002/bit.27359
13. 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
14. P. Zhao, J. George, B. Li, N. Amini, J.L. 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.
15. 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
16. 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
17. 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
18. J.L. Paluh (2016) Epigenetics, Ethnicity, Bioinformatics and Nanotechnology Opening Frontiers in Cardiac Medicine. International Journal of Stem Cell Research and Therapy 3:027. ISBN: 2469-570X
19. 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
20. 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
21. 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
22. 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.
23. 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
24. 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
25. 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
26. 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
27. 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.
28. 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
29. 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
30. 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
31. 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
32. 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
33. J.L. Paluh (2008) Sentinels of DNA integrity in stem cells. Cell Cycle 7(18): 2779-2780. DOI: 10.4161/cc.7.18.6890
34. J.L. Paluh (2008) Kinesin-14 leaps to pole position in bipolar spindle assembly. Chinese Journal of Cancer, 27(9): 1-5. PMID:18799042
35. 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
36. 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
37. 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
38. 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

Patents

• 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.