Lab members

Lee Rubin

HSCRB
Professor
Contact Info
lee_rubin@harvard.edu

Dr. Rubin received his Ph.D. in Neuroscience from The Rockefeller University and completed postdoctoral fellowships in Pharmacology from Harvard Medical School and in Neurobiology from Stanford University School of Medicine. He has worked both in academia and in industry.  Notably, at Athena Neurosciences (now Elan Pharmaceuticals), he initiated a project that lead to the discovery of an antibody that blocks lymphocyte trafficking across the BBB.  This work culminated in the development of an anti-integrin antibody, now known as Tysabri, which has been approved for treatment of multiple sclerosis.  Subsequently, he became Chief Scientific Officer of Ontogeny, Inc (now Curis, Inc), a biotechnology company in Cambridge, MA, founded by Dr. Douglas Melton. Dr. Rubin's work there centered on the hedgehog (Hh) pathway and its involvement in cancer and neurodegenerative disease.  Potent small molecule Hh antagonists were identified and partnered with Genentech where they were modified chemically, and, one, Erivedge, was recently approved as an oral treatment for invasive basal cell carcinoma. Numerous other phase II solid tumor studies are currently underway. 

Dr. Rubin is Professor of Stem Cell and Regenerative Biology at Harvard University and Director of Translational Medicine at the Harvard Stem Cell Institute.  Much of his effort is devoted to identifying therapeutics for orphan neural disorders such as Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis, using new kinds of stem cell-based screens. His lab also explores different chemical biology approaches for manipulating cell fate. Some of this work has been published recently in Cell, Cell Stem Cell, Nature Chemical Biology, Developmental Biology, and Science.

Selected Publications

  1. Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, Chen JW, Lee RT, Wagers AJ, Rubin LL. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 2014; 344:630-4.
  2. Sen A, Dimlich DN, Guruharsha KG, Kankel MW, Hori K, Yokokura T, Brachat S, Richardson D, Loureiro J, Sivasankaran R, Curtis D, Davidow LS, Rubin LL, Hart AC, Van Vactor D, Artavanis-Tsakonas S. Genetic Circuitry of Survival motor neuron, the gene underlying spinal muscular atrophy.  Proc Acad Natl Sci U S A 2013; 110:E2371-80. PMCID: PMC3696827.
  3. Yang YM, Gupta SK, Kim KJ, Powers BE, Cerqueira A, Wainger BJ, Ngo HD, Rosowski KA, Schein PA, Ackeifi CA, Arvanites AC, Davidow LS, Woolf CJ, Rubin LL. A Small Molecule Screen in Stem Cell-derived Motor Neurons Identifies a Kinase Inhibitor as a Candidate Therapeutic for ALS.  Cell Stem Cell 2013; 12:713-26. PMCID: PMC3707511.
  4. Ding HQ, Lee YK, Schaefer EA, Peters DT, Veres A, Kim K, Kuperwasser N, Motola DL, Meissner TB, Hendriks WT, Trevisan M, Gupta RM, Moisan A, Banks E, Friesen M, Schinzel RT, Xia F, Tang A, Xia Y, Figueroa E, Wann A, Ahfeldt T, Daheron L, Zhang F, Rubin LL, Peng LF, Chung RT, Musunuru K, Cowan CA. A Talen Genome-Editing System for Generating Human Stem Cell-Based Disease Models. Cell Stem Cell 2013; 12:238-51. PMCID: PMC3570604.
  5. Wang Y, Davidow L, Arvanites AC, Blanchard J, Lam K, Xu K, Oza V, Yoo JW, Ng JMY, Curran T, Rubin LL, McMahon AP. Glucocorticoid Compounds Modify Smoothened Localization and Hedgehog Pathway Activity. Chem Biol 2012; 19:972-82. PMCID: PMC3724998.
  6. Hayhurst, M, Wagner A, Cerletti M, Wagers AJ, Rubin LL. A cell-autonomous defect in skeletal muscle satellite cells expressing low levels of Survival of Motor Neuron protein. Dev Biol 2012; 368:323-34. PMCID: PMC3851302.
  7. Wang, Yu, Arvanites AC, Davidow L, Blanchard J, Lam K, Yoo JW, Coy S, Rubin LL, McMahon, AP. Selective Identification of Hedgehog Pathway Antagonists By Direct Analysis of Smoothened Ciliary Translocation. ACS Chem Bio 2012; 7:1040-8. PMCID: PMC3905677.
  8. Chen PC, Gaisina IN, El-Khodor BF, Ramboz S, Makhortova NR, Rubin LL, Kozikowski AP. Identification of a Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitor, BIP-135, that Prolongs the Median Survival Time of ∆7 SMA KO Mouse Model of Spinal Muscular Atrophy. ACS Chem Neurosci 2012;3:5-11. PMCID: PMC3279955.
  9. Annes JP, Ryu JH, Lam K, Carolan PJ, Utz K, Hollister-Lock J, Arvanites AC, Rubin LL, Weir G, Melton DA. Adenosine kinase inhibition selectively promotes rodent and porcine islet ß-cell replication. Proc Natl Acad Sci U S A 2012; 109:3915-20. PMCID: PMC3309788.
  10. Makhortova NR, Hayhurst M, Cerqueira A, Sinor-Anderson A, Zhao W-N, Heiser P, Arvanites AC, Davidow LS, Waldon ZO, Steen JA, Lam K, Ngo H, Rubin LL. A Screen for Regulators of Survival of Motor Neuron Protein Levels. Nature Chem Biol 2011; 7:544-52. PMCID: PMC3236614.
  11. Rubin LL, Haston KM. Stem cells and drug discovery. BMC Biol2011; 9:42. PMCID: PMC3110139.
  12. Tang JY, Li D, Reich M, Callahan CA, Fu L, Yauch RL, Wang F, Kotkow K, Chang KS, Shpall E, Wu A, Rubin LL, Marsters JC, Epstein EH, Caro I, de Sauvage FJ. Targeting Superficial or Nodular Basal Cell Carcinoma with Topically Formulated Small Molecule Inhibitor of Smoothened. Clinical Cancer Research2011; 17:3378-87. PMCID: PMC3113453.
  13. Haramati S, Chapnik E, Sztainberg Y, Eilam R, Zwang R, Gershoni N, McGlinn E, Heiser PW, Wills AM, Wirguin I, Rubin LL, Misawa H, Tabin CJ, Brown R Jr, Chen A, Hornstein E. miRNA malfunction causes spinal motor neuron disease. Proc Natl Acad Sci U S A 2010; 107:13111-6. PMCID: PMC2919953.
  14. Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, Haggarty SJ, Rubin LL, Peterson RT, Schier AF. Behavioral profiling links drugs to biological targets and the regulation of rest/wake states.  Science2010; 327:348-51. PMCID: PMC2830481. 
  15. Ichida JK*, Blanchard J*, Lam K*, Son EY*, Chung, JE, Dieter E, Loh KM, Carter AC, Di Girogio FP, Koszka K, Huangfu D, Huangfu D, Akutsu H, Liu DR, Rubin LL+, Eggan K+. A Small Molecule Inhibitor of Tfg-ß Signaling Replaces Sox2 in Reprogramming by Inducing Nanog. Cell Stem Cell 2009; 5:491-503. (* joint first authors; + joint senior authors). PMCID: PMC3335195.
  16. Chen S, Borowiak M, Fox JL, Maehr R, Osafune K, Davidow L, Lam K, Peng LF, Schreiber SL, Rubin LL, Melton DM. A small molecule that directs differentiation of human ESCs into the pancreatic lineage. Nature Chem Biol 2009; 5:258-65.
  17. Yauch RL, Gould SE, Scales SJ, Tang T, Tian H, Ahn CP, Marshall D, Fu L, Januario T, Kallop D, Nannini-Pepe M, Kotkow K, Marsters JC, Rubin LL, de Sauvage FJ. A paracrine requirement for hedgehog signaling in cancer. Nature 2008; 455:406-10.
  18. Brunton SA, Stibbard JH, Rubin LL, Guicherit OM, Kruse LI, Price S, di Lucrezia R, Mackinnon CH, Avery A, Park Y, Buxton D, Boyd EA. Potent agonists of the Hedgehog signaling pathway. Bioorg Med Chem Lett 2009; 19:4308-11.
  19. Rubin LL. Stem Cell and drug discovery: The beginning of a new era? Cell 2008, 132:549-52.
  20. Romer JT, Kimura H, Magdaleno S, Sasai K, Fuller C, Baines H, Connelly M, Stewart CF, Gould S, Rubin LL, Curran T. Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1+/- p53-/- mice. Cancer Cell, 6:229-40, 2004.
  21. Machold R, Hayashi S, Rutlin M, Muzumdar MD, Nery S, Corbin JG, Gritli-Linde A, Dellovade T, Porter JA, Rubin LL, Dudek H, McMahon AP, Fishell G. Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron, 39:937-50, 2003.
  22. Williams JA, Guicherit OM, Zaharian BI, Xu Y, Chai L, Wichterle H, Kon C, Gatchalian C, Porter JA, Rubin LL, Wang FY. Identification of a small molecule inhibitor of the hedgehog signaling pathway: Effects on basal cell carcinoma-like lesions. Proc Natl Acad Sci, 100:4616-21, 2003.
  23. Frank-Kamenetsky M, Zhang XM, Bottega S, Guicherit O, Wichterle H, Dudek H, Bumcrot D, Wang FY, Jones S, Shulok J, Rubin LL, Porter JA. Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists. J Biol, 1:10, 2002. PMCID: PMC137065.
Tim Ahfeldt

Tim Ahfeldt

HSCRB
Postdoctoral Fellow
Contact Info
timahfeldt@fas.harvard.edu

I study the role that transcription factors play in determining neuronal cell fate; in particular what discerns immature and mature neuronal subpopulations. I am interested in translational research that will use this knowledge in the differentiation of pluripotent stem cells into clinically relevant cell populations in an attempt to model human disease in vitro.

Tony Arvanites

Tony Arvanites

HSCRB
Manager, Cheminformatics
Contact Info
anthony_arvanites@harvard.edu
617-496-8299
Chen Benkler

Chen Benkler

HSCRB
Postdoctoral Fellow
Contact Info
cbenkler@fas.harvard.edu
Sean Buchanan

Sean Buchanan

HSCRB
Postdoctoral Fellow
Contact Info
sean_buchanan@harvard.edu
Lance Davidow

Lance Davidow

HSCRB
Director of Bioinformatics
Contact Info
lance_davidow@harvard.edu
617-495-4994

I specialize in image analysis for High Content Screening projects. We run several automated microscopes including a PerkinElmer Opera (confocal), an Operetta, a Cellomics ArrayScan and a Nikon BioStation CT (live imaging time course). We mostly use PerkinElmer Acapella image analysis software on the instruments or on the web-based Columbus platform.

Gustavo German

Gustavo German

HSCRB
Graduate student
Contact Info
gustavogerman@fas.harvard.edu
Kara Held

Kara Held

HSCRB
Lab Manager/Research Assistant
Contact Info
kara_held@harvard.edu
617-495-9188
Phylis Hetie

Phylis Hetie

HSCRB
Postdoctoral Fellow
Contact Info
phylis_hetie@harvard.edu
Geraldine Jowett

Geraldine Jowett

HSCRB
Research Assistant
Contact Info
gmjowett@fas.harvard.edu

Lida Katsimpardi

HSCRB
Postdoctoral Fellow
Contact Info
lida_katsimpardi@harvard.edu

Embryonic stem cell derived generation of sensory neurons.

Pain affects up to 20% of the population, so it constitutes both a scientifically challenging area as well as a major focus for drug discovery effort. In this scope, we are interested in developing a method to efficiently generate nociceptive (pain) neurons by using embryonic stem cells. By using various combinations of morphogens we have successfully generated a pure population of sensory neurons where nociceptors, proprioceptors and mechanoreceptors are uniquely present. Functional studies of these neurons are ongoing.

 

Regeneration of age-related decline in adult neurogenesis.

Aging is a non-reversible process that results in a decline of the organism’s function with time. As with all tissues, the brain progressively loses its regenerating potential. Our focus is to understand the mechanisms that underlie this phenomenon at the cellular level and find ways to reactivate the regenerative capacity of the aging brain cells.

Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, Chen JW, Lee RT, Wagers AJ, Rubin LL. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science 2014; 344:630-4.

Jane LaLonde

Jane LaLonde

HSCRB
Lab Administrator
Contact Info
jane_lalonde@harvard.edu
617-384-8105
Maureen Sherry Lynes

Maureen Sherry Lynes

HSCRB
Postdoctoral Fellow
Contact Info
maureen_sherry@harvard.edu

Survival of Motor Neuron Protein in Neural Differentiation

Survival of motor neuron protein (SMN) expression is lost in the childhood genetic disease spinal muscular atrophy (SMA).  I am using iPS lines derived from SMA patients to investigate the role of SMN in motor neuron differentiation as well as in differentiation to other neuron types.  I am also developing an imaged based assay using human iPS-derived neurons; this assay will be used in a screen to identify small molecules that elevate SMN in human neurons.

Nina Makhortova

HSCRB
Research Associate
Contact Info
nina_makhortova@harvard.edu

I am interested in finding a treatment of neurodegenerative disorders and currently working on childhood disease Spinal Muscular Atrophy. My research focus is to identify mechanisms that regulate levels of the survival motor neuron (SMN) protein. We have successfully executed an image-based screen of annotated chemical libraries to discover compounds that could increase cellular SMN and have identified the RTK-PI3K-AKT-GSK-3 as one of the most important signaling cascades. Currently I am conducting a microarray study of other key hit compounds from our screen and contemplating RNAi screen to find additional SMN regulators.  I am also involved in assay development of internal screening projects in Dr.Rubin’s laboratory.

Makhortova NR, Hayhurst M, Cerqueira A, Sinor-Anderson A, Zhao W-N, Heiser P, Arvanites AC, Davidow LS, Waldon ZO, Steen JA, Lam K, Ngo H, Rubin LL. A Screen for Regulators of Survival of Motor Neuron Protein Levels. Nature Chem Biol 2011; 7:544-52.

Jesse Mull

Jesse Mull

HSCRB
Research Assistant
Contact Info
jesse_mull@harvard.edu
Shiyan Ng

Shiyan Ng

HSCRB
Postdoctoral Fellow
Contact Info
shiyan_ng@harvard.edu
Erika Norabuena

Erika Norabuena

HSCRB
Research Assistant
Contact Info
enorabuena@fas.harvard.edu
Kent Nybakken

Kent Nybakken

HSCRB
Researcher
Contact Info
knybakken@fas.harvard.edu
617-495-1744
Naomi Tsujimoto Okugawa

Naomi Tsujimoto Okugawa

HSCRB
Research Associate
Contact Info
naomi_tsujimoto@harvard.edu
Alison O'Neil

Alison O'Neil

HSCRB
Postdoctoral Fellow
Contact Info
aoneil@fas.harvard.edu
Elizabeth Paik

Elizabeth Paik

HSCRB
Postdoctoral Fellow
Contact Info
elizabeth_paik@harvard.edu
Kathy Pfaff

Kathy Pfaff

HSCRB
Senior Research Manager
Contact Info
kathleen_pfaff@harvard.edu
617-496-1483
Feodor Price

Feodor Price

HSCRB
Postdoctoral Fellow
Contact Info
feodor_price@harvard.edu
Giuliana Repetti

Giuliana Repetti

HSCRB
Research Assistant
Contact Info
giuliana_repetti@harvard.edu
Alessandra Rigamonti

Alessandra Rigamonti

HSCRB
Postdoctoral Fellow
Contact Info
alessandra_rigamonti@harvard.edu
Natalia Rodriguez Muela

Natalia Rodriguez Muela

HSCRB
Postdoctoral Fellow
Contact Info
natalia_rodriguezmuela@harvard.edu
Hye Young Shin

Hye Young Shin

HSCRB
Postdoctoral Fellow
Contact Info
hyeyoungshin01@fas.harvard.edu


Chicheng Sun

Chicheng Sun

HSCRB
Postdoctoral Fellow
Contact Info
chichengsun@fas.harvard.edu
Chen Wu

Chen Wu

HSCRB
Postdoctoral Fellow
Contact Info
chenwu@fas.harvard.edu

I am looking for a novel and specific drug to improve the survival of motor neurons for ALS therapeutics. By studying the targets of the drug, we hope to explain the mechanism and how the downstream signal pathways work.

Aya Alame

Aya Alame

HSCRB
Undergraduate student
Contact Info
aalame@college.harvard.edu
Danielle Reny

Danielle Reny

HSCRB
Undergraduate student
Contact Info
daniellereny@college.harvard.edu