- 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 biology
- Neuroscience Nanotechnology- CNS Neurodegeneration, Spinal cord injury
- Nanotechnology and 3D Tissue Engineering
- Computational Modeling of Biological Networks
- Disease complexity- Aging and Ethnicity
- Cancer Biology- Cell Cycle, Mitosis, Drug discovery
- Biological control and Self-assembling systems-Nanomotors, MTOCs
Research in Dr. Paluh's lab applies tools of nanotechnology to understand biological self-assembly mechanisms from intracellular machines to complex multi-cellular tissue and organ architectures. This encompasses natural assembly and design principles as well as perturbations to these systems or functional biomimicry. The molecular machines of the eukaryotic microtubule cytoskeleton play critical roles in cell proliferation and genome stability as well as in the structure and function of complex differentiated cell types and tissues, including specialized neural architectures of the brain. We apply our knowledge of the eukaryotic cytoskeleton to cancer biology and to human stem cell biology to understand differentiation into specialized cell types and assembly of these specialized cells into 3D tissues with functional complexity. 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.
My lab has made fundamental contributions to understanding microtubule mechanisms and to human stem cell biology. The former include 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 models. The upstream site of action makes this regulator of particular interest in targeting a broad range of drug resistant cancers.
In human stem cell biology, my laboratory applies nanotechnology, epigenetic reprogramming and 3D tissue engineering along with bioinformatics analysis of whole genome transcriptome, microRNA, and histone epigenetic profiling to understand multilineage development, tissue differentiation and epigenetic triggers to malfunction. Nanotechnology, custom photolithography and microfluidics allow us to design high throughput microarrays, microsieves, patterning platforms and cell-scaffolds. Stem cell studies are supported in part by New York State via NYSTEM. Current and past collaborative efforts include cancer research (breast, pancreatic and glioma), cardiogenesis, brain tissue models of aging and neurodegeneration using3D neural-glia co-cultures, and computational models of nanocommunication including hybrid neuron-computer interfaces. Our work applies nanotechnology and 3D tissue engineering, human somatic, cancer and stem cell biology, timelapse 3D microscopy, biochemistry, yeast genetics, molecular biology, bioinformatics, computational modeling and structural and systemic approaches.
Cellular Machines: Function & NanoEngineering of the Microtubule Cytoskeleton
- 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 develop hybrid programmable adaptable nano-microsystems.
- Kinesin-like proteins (Klps) and Microtubules in Transport Mechanisms. Klps act as master regulators of microtubule cytoskeleton structure and function including roles in cargo transport, network signaling and cytoskeleton remodeling providing polarized specialized platforms critical to eukaryotic cells. At least fourteen conserved Klp families exist, but in varied combinations in eukaryotes indicating inherent flexibility in motor protein task relationships. Work from the Paluh lab is defining functional domain determinants of Klps and tubulins fundamental to understanding Klp-Tubulin-Microtubule complexes and to their use in designed bioengineering applications.
- The γ-TuRC MTOC and γ-tubulin Complexes. The Microtubule Organizing Center (MTOC) is a macromolecular complex and the site of microtubule growth, polarized organization and dynamics as well as a scaffold and signaling hub. 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.
- Asymmetric Processes & Checkpoints. Cells avoid fatal system failures that can lead to cell, tissue or organism death by adjusting cell cycle progression to allow time for error correction. So-called checkpoints overlay cellular mechanisms to provide this fail-safe mechanism. In multi-cellular eukaryotes checkpoints may ‘time out’ due to the greater consequences of a failed restart. Research in the Paluh lab investigates interlinked checkpoint and asymmetry mechanisms in mitosis. Asymmetry in development helps to define daughter cell fates and understanding these mechanisms will aid in design of synthetic 4D spatiotemporal cellular niches.
Multicellular Design Principles in Human Development and Disease
- Development of Optimized Synthetic 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 4D architectures that mimic the cellular environment in a spatiotemporally reactive manner. The Paluh lab is applying nanotechnology tools towards developing functionalized hydrogel scaffolds, cell patterning approaches and complex multi-cell type 3D tissue engineering.
- Human Pluripotent Stem Cells (hESCs and hiPSCs). Human stem cell biology offers unlimited potential for human therapies. Work in the Paluh lab has expanded information on embryoid body (EB) stem cell intermediates, multilineage differentiation and characterization, and applications to human aging diseases such as cancer and neurodegeneration. Limited ethnic diversity in stem cell lines was addressed in part by a ~$1M NYSTEM award for derivation, in vivo teratoma and in vitro differentiation analysis, and whole genome characterization of transcriptome, microRNAs, and histone epigenetic modifications. This latter work with stem cell expert Dr. J. Cibelli Michigan State University, included bioinformatics analysis by Dr. M. Buck, SUNY Buffalo and Dr. H. Otu, U. Nebraska-Lincoln. The lines will be banked for scientific community, biomedical and industry use and followed NYSTEM, ISSCR and National Academy of Science guidelines.
- Nuclear Reprogramming (hiPSCs). The generation of induced pluripotent stem cells (iPSCs) provides an opportunity to understand key genetic and epigenetic requirements in normal and diseased tissues. The Paluh lab is using ED-iPSCs to investigate aging and neurodegeneration, cancer, and cardiogenesis in normal and disease development.
Integrating Biology-Inspired Information Theory and Computational Modeling
- Nanoscale Communication. To understand and manipulate nanoscale networks and promote innovation, Dr. Paluh participates on the IEEE Standards Association P1906.1 Working Group on Recommended Practice for Nanoscale and Molecular Communication Framework, which applies Shannon’s Rules of Communication to hybrid biological and human made systems. In addition Dr. Paluh is part of the Cell to Macroscale Working Group of the NIH IMAG MSM Interagency Modeling Analysis Group and Multiscale Modeling efforts that supports use of mathematical computational modeling of biological processes to promote biomedical advances.
- Computational Modeling of Neural Functions. Recent collaborations are applying biological model systems in NEMS and MEMS devices with computational neuroscience to address the neural biological-computer interface. The longterm goal is to design new methods to record and monitor subtle changes in intracellular neural signaling and determine their temporal impact on larger tissue functions with particular applications to brain research.
Selected Professional Contributions
- Editorial Board, Scientific Reports, Nature publishing
- 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
- 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, in press.
- 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
- 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
- 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.