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 a broad experience in both academia and industry, particularly in the realms of cell-based assays and drug discovery. Prior to coming to Harvard, he was Chief Scientific Officer of Curis, Inc., a Cambridge-based biotechnology company, where his group identified the first small molecule regulators of the hedgehog signaling pathway. One of their antagonists was developed by Genentech and is now (as Erivedge) approved as the first oral treatment for metastatic basal cell carcinoma. At Harvard, much of his work is focused on finding key molecular mediators of different neurodegenerative diseases and on searching for effective preclinical therapeutic candidates. His group's research takes advantage of their ability to produce large numbers of patient-derived induced pluripotent stem cell lines and of effective means of deriving large numbers of differentiated neurons from them. They have set up an array of techniques that allow them to identify early cellular and physiological changes in neurons as they become diseased. For example, they have identified new targets for the treatment of the motor neuron disorders Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis. They are also studying Autism Spectrum Disorders, Parkinson’s disease and Alzheimer’s disease. Recently, his group discovered that a circulating protein, GDF11, has the ability to reverse some of the changes in the CNS associated with aging. They are actively exploring the therapeutic implications of these observations as well.

Selected Publications

  1. Wainger BJ, Buttermore ED, Oliveira JT, Mellin C, Lee S, Saber WA, Wang A, Ichida JK, Chiu IM, Barrett L, Huebner EA, Bilgin C, Tsujimoto N, Brenneis C, Kapur K, Rubin LL, Eggan K, Woolf CJ. Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts. Accepted Nature Neuroscience 2014.
  2. Schlaeger, TM, Daheron L, Brickler TR, Entwisle S, Chan K, Cianci A, DeVine A, Ettenger A, Fitzgerald K, GodfreyM, Gupta D, McPherson J, Malwadkar P, Doi A, Jung N, Li X, Lynes MS, Brookes E, CherryABC, Demirbas D, TsankovA, Zon LI, Rubin LL, Feinberg AP, Meissner A, Cowan CA, and Daley GQ. A comparison of non-integrating reprogramming methods. Nature Biotech 2014 Nov 24. doi: 10.1038/nn.3886. [Epub ahead of print].
  3. Woodard CM, Campos BA, Kuo S-H, Nirenberg MJ, Nestor MW, Zimmer M, Mosharov E, Sulzer D, Zhou H, Paull D, Clark L, Schadt EE, Sardi SP, Rubin L, Eggan K, Brock M, Lipnick S, Rao M, Chang S, Li A, Noggle SA. iPSC-Derived Dopamine Neurons Reveal Differences between Monozygotic Twins Discordant for Parkinson’s Disease. Cell Reports 2014; 9:1-10.
  4. Blum B, Roose AN, Barrandon O, Maehr R, Arvanites AC, Davidow LS, Davis JC, Peterson QP, Rubin LL, Melton DA. Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway. eLife 2014; 3:e02809
  5. French A, Suh JY, Suh CY, Rubin L, Barker R, Bure K, Reeve B, Brindley DA. Global strategic partnerships in regenerative medicine. Trends Biotechnol 2014; 32:436-40.
  6. Cherry JJ, Kobayashi DT, Lynes MM, Naryshkin NN, Tiziano FD, Zaworski PG, Rubin LL, Jarecki J. Assays for the identification and prioritaztion of drug candidates for spinal muscular atrophy. Assay Drug Dev Technol 2014; 12:315-41.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. Rubin LL. Stem Cell and drug discovery: The beginning of a new era? Cell 2008; 132:549-52.
  20. 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 2002; 1:10. 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.

Chen Benkler

Chen Benkler

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

Sean Buchanan

HSCRB
Researcher
Contact Info
sean_buchanan@harvard.edu
Diego Cordero

Diego Cordero

HSCRB
Fellow
Contact Info
diego_cordero@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
Tobias Grass

Tobias Grass

HSCRB
Graduate student
Contact Info
tobiasgrass@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

I am working on in vitro human stem cell models of neurodegenerative diseases. I am currently focused on Parkinson’s disease, studying the effects of different transcription factors and clinically relevant genomic mutations on neuronal cell fate.

Lida Katsimpardi

HSCRB
Research Associate
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

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
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

I am interested in adult stem cell function and the mechanisms that regulate stem cell fate. I study a skeletal muscle stem cell  - the satellite cell which is responsible for postnatal muscle regeneration. Our group focuses on translational research with an eye towards how satellite cells are affected in disease - specifically spinal muscular atrophy (SMA). In addition I am curious to know whether or not satellite cell function can be augmented in a pharmacological manner.

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

I am interested in characterizing the mechanisms that govern the degradation of Survival of Motor Neuron protein (SMN). Once that is established, the next step of my research focus is on finding compounds that, by specifically inhibiting these pathways, promote the stabilization of the protein and increase motor neuron survival. The ultimate goal of this project is to discover compounds than would potentially lead to new therapeutics for treating patients with Spinal Muscular Atrophy (SMA). I am also studying the role that SMN plays in controlling motor neuron death outside the SMA context in vivo.

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

I joined the Rubin lab in September 2013 as a postdoctoral fellow and have been working on functional characterization of human iPSC-derived motor neurons. I am interested in modeling CNS diseases in vitro and discovering novel drug candidates by approaches like electrophysiology, calcium imaging, genome editing, and small molecule phenotypic screening.

I received my BS in Biological Sciences at Tsinghua University in 2007 and PhD in Cell and Developmental Biology at the Pennsylvania State University, University Park, in May 2013. In graduate school, I studied the function of a synaptic cell adhesion molecule in neuronal maturation and psychiatric disorders under the guidance of Dr. Gong Chen.

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
Shannon Fan

Shannon Fan

HSCRB
Undergraduate student
Contact Info
shannonfan@college.harvard.edu
Rachel Halperin

Rachel Halperin

HSCRB
Undergraduate student
Contact Info
rachelhalperin@college.harvard.edu
Dani Keahi

Dani Keahi

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

Danielle Reny

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