Lab members

Jeffrey Macklis

Jeffrey Macklis

HSCRB
Max and Anne Wien Professor of Life Sciences, Harvard University; Professor of Neurology and of Neurosurgery, Harvard Medical School
Contact Info
jeffrey_macklis@harvard.edu

Jeffrey D. Macklis

Max and Anne Wien Professor of Life Sciences
Department of Stem Cell and Regenerative Biology
  and
Center for Brain Science
Harvard University

Professor of Neurology and of Neurosurgery, Harvard Medical School

Principal Faculty and Executive Committee
  and Neuroscience / Nervous System Diseases Program
Harvard Stem Cell Institute, Harvard University

Jeffrey D. Macklis’ laboratory is directed toward both 1) understanding molecular controls and mechanisms over neuron sub-type specification, development, axon guidance-circuit formation, and degeneration in the cerebral cortex (e.g. CSMN in ALS, HSPs, and PLS; CStrPN in HD), and 2) applying developmental controls toward both brain and spinal cord regeneration (e.g. corticospinal motor neuron (CSMN) circuitry that degenerates in ALS and other “upper motor neuron” degenerative diseases, and whose injury is central to loss of motor function in spinal cord injury) and directed differentiation for in vitro therapeutic and mechanistic screening. The lab focuses on neocortical projection neuron development and sub-type specification; neural progenitor / “stem cell” biology; induction of adult neurogenesis (the birth of new neurons); subtype-specific axonal growth cone biology; and directed neuronal subtype differentiation via molecular manipulation of neural progenitors and pluripotent cells (ES/iPS). The same biology informs understanding of neuronal subtype specificity of human neurodegenerative and developmental diseases, in particular ALS / motor neuron disease, HSPs, PLS, Huntington's disease, autism spectrum disorders (ASD), and Rett syndrome and ACC in particular of ASDs.

Macklis is the Max and Anne Wien Professor of Stem Cell and Regenerative Biology, Harvard University, and Professor of Neurology [Neuroscience] and of Surgery [Neurosurgery] at Harvard Medical School (HMS); member of the Center for Brain Sciences at Harvard University; Executive Committee member of the Harvard Stem Cell Institute; former founding Director of the MGH-HMS Center for Nervous System Repair (2001-2011); founding Program Head, Neuroscience / Nervous System Diseases, Harvard Stem Cell Institute, Harvard University (2004-2013); and Neurobiologist and Neurologist at Massachusetts General Hospital (MGH). He is a faculty member in the Harvard University graduate Programs in Neuroscience, Developmental and Regenerative Biology, and Biological and Biomedical Sciences; M.D.-Ph.D. Program; and Molecular and Cellular Biology / MCO program; and of the affiliated faculty of the Harvard-Massachusetts Institute of Technology (M.I.T.) Division of Health Sciences and Technology (HST), and the M.I.T. faculty within HST.

He attended M.I.T. (S.B. Bioelectrical Engineering; S.B. Literature), Harvard Medical School (Harvard-M.I.T. HST Program), and graduate school at M.I.T. within the Harvard-M.I.T. Division of Health Sciences and Technology (HST), a graduate student with Richard L. Sidman. He was a postdoctoral fellow in developmental neuroscience with Richard Sidman at HMS, where he also trained clinically in Internal Medicine at Brigham and Women’s Hospital (BWH) and adult neurology in the Harvard-Longwood Neurological Training Program. Until moving his laboratory to MGH in 2001/2 to direct the thematic MGH-HMS Center for Nervous System Repair, he was in the basic science Division of Neuroscience at Children’s Hospital, HMS, and was Co-Director of the Parkinson’s Disease and Related Disorders Program at Brigham and Women’s Hospital / HMS. He assumed his current position at Harvard University in Cambridge in 2007, and moved physically in 2011.

Dr. Macklis is the recipient of a number of awards and honors, including a Rita Allen Foundation Scholar Award, a Director’s Innovation Award from the NIH Director’s Office, a Soderberg Prize Symposium Lectureship at the Swedish Society for Medicine, The CNS Foundation Award, Pearlstein Scholar Award, Seidman Award in CNS Research, several Hoopes Prizes for excellence in undergraduate research mentoring, and a Senator Jacob Javits Award in the Neurosciences and MERIT Award from the NINDS/NIH.

Karen Yee

HSCRB
Lab Manager
Contact Info
karen_yee@harvard.edu

Karen Yee

Dartmouth College, A.B. (Biology); University of Washington, Ph.D. (Molecular and Cellular Biology)

I joined the Macklis lab in the spring of 2011. I serve as the research lab manager and am in charge of maintaining the operations of the lab. This involves negotiating with vendors, ordering and receiving lab equipment and supplies; identifying and assisting in resolving any problems with space, equipment and personnel; and serving as the safety officer for the lab and ensuring that laboratory personnel and laboratory space are compliant with training and all safety regulations. I also oversee the mouse colony and handle most of the administrative responsibility of the colony including ordering animals and maintaining the animal protocols and COMS approvals.

Previously, I was an Instructor/Research Lab Manager in the Dept. of Pathology at Beth Israel Deaconess Medical Center, I designed and carried out experiments to demonstrate that vascular endothelial growth factor B potently increases connexin 43 expression in neonatal rat cardiac myocyte gap junctions by activating VEGFR1, stimulating a signaling pathway that includes PI3Kinase and Map Kinase and increasing trafficking of Cx43 to gap junctions via microtubules. I also directed laboratory operations for a small lab (4-6 people) and maintained a mouse colony (50+ cages).

As a Post-Doctoral Fellow in the Dept. of Pathology, Division Tumor Biology/Angiogenesis at Beth Israel Deaconess Medical Center, I oversaw numerous projects characterizing the role of Thrombospondin-1 (TSP-1), a potent anti-angiogenic, anti-tumorigenic factor, in various mouse models of cancer. I established collaborations with members in the lab and groups outside the lab to develop and characterize three different mouse models of cancers that involved the molecule TSP-1: a) I initiated, developed and characterized a transgenic mouse model for breast cancer in order to study how TSP-1 affects tumor progression at different stages (i.e. initiation to metastasis), b) I Initiated a collaboration to test whether interperiotenal injections of a compound (halofuginone) or recombinant peptides against TSP-1 would inhibit mammary tumor progression in a mouse model of breast cancer, c) I identified overlapping and non-overlapping functions for TSP-1 and integrin αvβ6 by comparing the phenotype in three different lines of transgenic mice.

As Graduate Student in the Molecular and Cellular Biology Program at the University of Washington, I determined that the integrin α5β1 and matrix molecule fibronectin were important in human smooth muscle cell contraction of fibrin clots and adhesion to fibrin clots. I also demonstrated that smooth muscle cells express both α5β1 and fibronectin on their surfaces and these proteins can act as bridge molecules between the cell and the fibrin matrix. I also collaborated with others in the lab to determine the integrin and fibrin expression patterns in diseased vessels.

Yee KO, Connolly CM, Duquette M, Kazerounian S, Washington R & Lawler, J. The Effect of Thrombospondin-1 on Breast Cancer Metastasis. Breast Cancer Research and Treatment epub April 13, 2008; 2009; 114(1): 85-96.

Yee KO, Connolly CM, Pines M. & Lawler J. Halofuginone inhibits mammary tumor growth in the polyoma middle T antigen mouse via a thrombospondin-1 independent pathway. Cancer Biology & Therapy 2006; 5(2): 218-224.

Ludlow A*, Yee KO*, Lipman R., Bronson R., Weinreb P., Sheppard D, Huang X. and Lawler J. Characterization of integrin 6 and thrombospondin-1 double null mice. Journal of Cellular and Molecular Medicine 2005; 9(1): 421-437.

Yee KO, Streit M, Hawighorst T, Detmar M & Lawler J. Expression of the type-1 repeats of thrombospondin-1 inhibits tumor growth through activation of TGF- . American Journal of Pathology 2004; 165(2): 541-552.

Ikari Y, Yee KO & Schwartz SM. Role of alpha5beta1 and alphavbeta3 integrins on smooth muscle cell spreading and migration in fibrin gels. Thrombosis and Haemostasis 2000; 84:701-705.

Ikari Y, Yee KO, Hatsukami TS, & Schwartz SM. Human Carotid Artery Smooth Muscle Cells Rarely Express alpha(v)beta3 integrin at sites of recent plaque rupture. Thrombosis and Haemostasis 2000;84:338-344.

Ikari Y, Fujikawa K, Yee KO & Schwartz SM. Alpha (1)-proteinase inhibitor, Alpha (1)-antichymotrypsin or Alpha (2)-macroglobulin is required for vascular smooth muscle cell spreading in three dimensional fibrin gels. Journal of Biological Chemistry 2000; 275:12799-12805.

Yee KO, Ikari Y, Bodary S, & Schwartz SM. Kistrin inhibits human smooth muscle cell interaction with fibrin. Thrombosis Research 2000; 97:39-60.

Yee KO, Rooney MM, Giachelli CM, Lord ST, & Schwartz SM. Role of 1 and 3 integrins in human smooth muscle cell adhesion to and contraction of fibrin clots. Circulation Research 1998; 83:241-251.

Detrich HW-3rd, Kieran MW, Chan FY, Barone LM, Yee K, Rundstadler JA, Pratt S, Ransom D, & Zon LI. Intraembryonic hematopoietic cell migration during vertebrate development. Proc. Natl. Acad. Sci. USA 1995; 92:10713-10717.

Sánchez I, Hughes RT, Mayer BJ, Yee K, Woodgett JR, Avruch J, Kyriakis JM, & Zon LI. Role of SAPK/ERK Kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature 1994; 372:794-798.

Kelley C, Yee K, Harland R, & Zon LI. Ventral expression of GATA-1 and GATA-2 in the Xenopus embryo defines induction of hematopoietic mesoderm. Developmental Biology 1994;165:193-205.

Yashar BM, Kelley C, Yee K, Errede B, & Zon LI. Novel members of the mitogen-activated protein kinase activator family in Xenopus laevis. Molecular and Cellular Biology 1993;13:5738-5748.

Yee K, Bishop TR, Mather C, & Zon LI. Isolation of novel receptor tyrosine kinase cDNA expressed by developing erythroid progenitors. Blood 1993;82:1335-1343.

Zon LI, Yamaguchi Y, Yee K, Albee EA, Kimura A, Bennett JC, Orkin SH, & Ackerman SJ. Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: Potential role in gene transcription. Blood 1993;81:3234-3241.

Galton VA, Morganelli CM, Schneider MJ, & Yee K. The role of thyroid hormone in the regulation of hepatic carbamyl phosphate synthetase activity in Rana catesbeiana. Endocrinology 1991;129:2298-2304.

Reviews:

Yee KO & Schwartz SM. Why atherosclerotic vessels narrow: The fibrin hypothesis. ISTH Congress State-of-the-Art Book. Thrombosis and Haemostasis 1999;82:762-771.

Yee KO & Schwartz SM. Why atherosclerotic vessels narrow and re-narrow (Chapter 5). In: Robert R. Ruffalo, Jr and Frank Walsh, eds. Apoptosis in Health and Disease. CRC Press, Amsterdam. 2000.

Yee KO, Ikari Y, & Schwartz SM. An update of the Grutzbalg Hypothesis: The role of thrombosis and coagulation in atherosclerotic progression. Thrombosis and Haemostasis. 2001 85:207-217.

Yee KO, Duquette M, Ludlow A, Lawler J. Purification and analysis of thrombospondin-1 (Basic Protocol). In: Bonifacino JS, Dasso M, Harford JB, Lippinscott-Schwartz J, Yamada KM, eds. Current Protocols in Cell Biology. John Wiley and Sons, Inc, New York. 2003 chapter 10, unit 10:10.

Ren B, Yee KO, Lawler JW and Khosravi-Far R. Regulation of tumor angiogenesis by thrombospondin-1. Biochim Biophys Acta, 2006; 1765(2):178-188.

Yee KO and Lawler JW. Regulation of angiogenesis and tumor growth by thrombospondin-1. In: Jakowlew SB, editor. Transforming Growth Factor-beta in Cancer Therapy. The Humana Press, Inc., New Jersey, 2006.

Kazerounian, S, Yee KO, Lawler JW. Thrombospondins in Cancer. Cell Mol Life Sci. 2008 65(5):700-712.

Ottaviano PG and Yee KO. Communication signals between cardiac fibroblasts and cardiac myocytes. J Cardiovasc Pharmacol. 2011 57(5):513-521.

Kelly Deneen

Kelly Deneen

HSCRB
Faculty Assistant
Contact Info
kelly_deneen@harvard.edu

Kelly Deneen

Boston College, B.A. (History, Black Studies); Simmons College, M.S. (Library and Information Science)

I joined the Macklis Lab in early 2011 as Dr. Macklis' Faculty Assistant. Prior to my arrival in the lab, I worked for several years at the Boston College Law Library, first as a Law Library Assistant and then as an Administrative Assistant to the Associate Dean for Library and Technology Services. During this time, I earned my M.S. in Library and Information Science from Simmons College. Boston College is where I earned my B.A. in History and Black Studies (now African and African Diaspora Studies).

In addition to my work at Harvard, I am a Teen Services Librarian at the Watertown Free Public Library.

Luciano Custo Greig

Luciano Custo Greig

HSCRB
Graduate Student, Harvard University Biological and Biomedical Sciences program
Contact Info
luciano_custogreig@hms.harvard.edu

Luciano Custo Greig

Yale University, B.S., M.S. (Molecular, Cellular, and Developmental Biology)

I am an MD student at Harvard Medical School and a PhD candidate in the Biological and Biomedical Sciences program at the Harvard Graduate School of Arts and Sciences. Since joining the Macklis lab in the fall of 2009, I have been investigating the functions of two transcription factors that control neocortical projection neuron differentiation in collaboration with Mollie Woodworth. Projection neurons establish the basic framework of long-range connections between different areas of the neocortex and between the neocortex and subcortical structures. I am particularly interested in corticospinal motor neurons (CSMN), large pyramidal neurons that reside in layer V of primary motor cortex and extend axons to the spinal cord to initiate voluntary movement. CSMN are clinically important because they are damaged in spinal cord injury and degenerate in amyotrophic lateral sclerosis (ALS) and related upper motor neuron diseases. I hope that our research will inform new therapeutic strategies to repair damaged circuits by generating replacement neurons in vitro or by recruiting endogenous precursors to produce them in vivo.

Prior to starting my graduate studies at Harvard, I attended Yale University, where I completed B.S. and M.S. degrees in Molecular, Cellular and Developmental Biology. During my M.S. thesis in the laboratory of Elke Stein, I studied netrin receptor function during cerebellar development and signaling pathways these receptors utilize to control cytoskeletal growth cone dynamics.

Alexander Murphy

Alexander Murphy

HSCRB
Graduate Student, Harvard University Program in Neuroscience
Contact Info
murphy2@fas.harvard.edu

Alexander Murphy

MIT, S.B. (Nuclear Engineering)

I joined the Macklis lab in the summer of 2011 as a graduate student in Neurobiology. My research interests center on elucidating molecular wiring mechanisms that guide projection neuron axons to diverse, distant targets with remarkable precision. I graduated from MIT in June 2010 with my degree in Nuclear Engineering, and worked as an undergraduate in Susumu Tonegawa's lab at the Picower Institute investigating local protein synthesis and capture in hippocampal spines.

Zhaoying Xu

Zhaoying Xu

HSCRB
Graduate Student, Harvard University Program in Neuroscience
Contact Info
zhaoyingxu@fas.harvard.edu

Zhaoying Xu

Grinnell College, B.A. (Biological Chemistry, Neuroscience)

I joined the Macklis lab in the summer of 2012 as a Ph.D. student in the Program in Neuroscience at Harvard. My research interests focus on the molecular and developmental controls over the specification and differentiation of corticostriatal projection neurons (CStrPN), which are the central neuronal population affected in Huntington’s disease.

Prior to beginning my studies at Harvard, I graduated from Grinnell College in May 2011 with a bachelor degree in Biological Chemistry and a concentration in Neuroscience, working with Professor Leslie Gregg-Jolly on regulation of DNA damage responses in prokaryotes Acinetobacter. In addition, I worked as an undergraduate in David Miller’s lab at Vanderbilt studying the neuronal wiring specificity in the C. elegans motor circuit and in Leslie Vosshall’s lab at Rockefeller investigating the molecular basis of post-fasting feeding responses in Drosophila.

Kadir Ozkan

HSCRB
International Ph.D. Student, Bogazici University
Contact Info
kadir_ozkan@harvard.edu

Kadir Ozkan

Middle East Technical University, B.S. (Molecular Biology and Genetics)

I joined the Macklis Lab in November 2010 as a visiting graduate student from Bogazici University, Istanbul. Working in close collaboration with Hari Padmanabhan, we aim to develop approaches for cellular repair of complex cortical circuitry, particularly corticospinal motor circuitry which degenerates in Amyotrophic Lateral Sclerosis (ALS) and is damaged by spinal cord injury. Specifically, we aim to activate key developmental transcriptional programs in progenitor cells of the postnatal brain, to direct these cells into specific neuronal subtypes. We are also interested in the transcriptional regulation of progenitors following the neurogenesis-to-gliogenesis switch in late embryonic development, to enable better manipulation of postnatal progenitor cells.

Prior to beginning my studies at Harvard, I received my BS degree in Molecular Biology and Genetics from Middle East Technical University (METU) in Ankara, and my MS degree from Bogazici University, Istanbul.  For my master's thesis, under the supervision of Prof. A. Nazli Basak, I worked on temporal expression analysis of angiogenesis-related genes in brain development. I also worked in Prof. Turker Kilic’s lab at the Marmara University on anti-angiogenic therapy approaches for brain tumors and arteriovenous malformations.

Previous Publications:

1. Ozduman K, Ozkan A, Yildirim O, Pamir MN, Gunel M, Kilic T, “Temporal expression of angiogenesis related genes in developing neonatal rodent retina: A novel in vivo model to study cerebral vascular development”, Neurosurgery, 66(3):538-43, 2010

2. Sun HI, Akgun E, Bicer A, Ozkan A, Kurtkaya O, Koc DY, Pamir MN, Kilic T, “Expression of angiogenic factors in craniopharyngiomas: implications for tumor recurrence”, Neurosurgery, 66 (4), 1-7, 2010

3.Toktas ZO, Akgun E, Ozkan A, Bozkurt SU, Bekiroglu N, Seker A, Konya D, Kilic T, “Relationship of angiogenic potential with clinical features in cranial meningiomas: a corneal angiogenesis study”, Neurosurgery, 67(6):1724-32, 2010

Maria Jose Galazo

HSCRB
Postdoctoral Fellow
Contact Info
maria_galazo@harvard.edu

Maria Jose Galazo

Autonoma University of Madrid, Ph.D.

My general research interest lies in the developmental biology of the cerebral cortex, especially in the assembly of cortical networks, and more recently in the potential application of developmental biology studies to re-formation of neuronal circuits. 

During my Ph.D at the Medical School of the Autonoma University of Madrid, I studied the anatomical distribution of the Reelin protein in different philogenetic groups like primate, carnivores and rodents, and its potential role in the developing and adult brain. Also, I studied the establishment and maintenance of the connections from the matrix neurons in the thalamus to the cortex, during the embryonic and postnatal life, and the interaction with intrinsic cortical circuits and feed-back cortical circuits to the thalamus. 

I joined the Macklis Lab in July 2007, and since then I have been working in collaboration with Dr. Jason Emsley, in describing the role of a transcriptional regulator that is critical for the development of cortico-thalamic projection neurons. My research goal is to study molecular-genetic controls over the specification and differentiation of cortico-thalamic neurons, specifically the two different components of the cortico-thalamic circuits, as well as some work on corticospinal motor neurons. This projection systems provide the main sensory-motor control output and the main motor output and from the cerebral cortex, respectively.

Key Recent Publications

  • Jabaudon D, Shnider S, Tischfield D, Galazo MJ, Macklis JD. 2011 "ROR{beta} Induces Barrel-like Neuronal Clusters in the Developing Neocortex." Cereb Cortex [Epub ahead of print; Jul 28]

Previous Publications

  • Rubio-Garrido, P., Pérez-de-Manzo, F., Porrero, C., Galazo, M.J., Clasca F. 2009 "ThalamicInput to Distal Apical Dendrites in Neocortical Layer 1 Is Massive and Highly
    Convergent." Cerebral Cortex. Feb 2. [Epub ahead of print]
  • Galazo, M.J., Martinez-Ceredeno, V., Porrero, C., Clasca, F. 2008. "Embryonic and Postnatal Development of the Layer I-Directed (“Matrix”) Thalamocortical System in the Rat." Cerebral Cortex. Feb;18(2):344-63.
  • Ramos-Moreno, T., Galazo, M.J., Porrero, C., Martinez-Ceredeno, V., Clasca, F. 2006. Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain. European Journal of Neuroscience. Jan 23 (2): 401-22.
  • Martinez-Cerdeno, V., Galazo, M.J., Clasca, F. 2003. "Reelin-immunorreactive neurons, axons, and neuropil in the adult ferret brain: evidence for axonal secretion of reelin in long axonal pathways." Journal of Comparative Neurology. Aug 11, 463 (1): 92-116.
  • Martinez-Cerdeno, V., Galazo, M.J., Cavada, C., Clasca, F. 2002. "Reelin immunoreactivity in the adult primate brain: intracellular localization in projecting and local circuit neurons of the cerebral cortex, hippocampus and subcortical regions."Cerebral Cortex. Dec 12 (12): 1298-1311.

Jessica MacDonald

HSCRB
Postdoctoral Fellow
Contact Info
jessica_macdonald@harvard.edu

Jessica MacDonald

University of British Columbia, Ph.D.

My general research interests lie in understanding the molecular regulation of the specification and stage-specific development of neurons. During my Ph.D. at the University of British Columbia, I focused on the role of DNA methylation and down-stream transcriptional regulators in regulating distinct transitional stages of neuronal differentiation during postnatal neurogenesis of olfactory receptor neurons.

Since joining the Macklis lab in August 2008, I have been working in close collaboration with Ryann Fame to examine the molecular-genetic controls over callosal projection neuron (CPN) specification and diversity. CPN, a distinct subtype of excitatory cortical projection neuron, connect the two hemispheres of the brain through the corpus callosum, disruptions of which have been implicated in autism spectrum disorders. We have identified a combinatorially-expressed set of genes that both define CPN as a broad population, and identify novel subpopulations of CPN during embryonic and postnatal development (Molyneaux, Arlotta, J NSci, ‘09), and we are now characterizing the function of a select, focused set of newly identified candidate genes in the development of CPN as a population, as well as distinct subtypes of CPN. Currently, little is known about the molecular development and heterogeneity of CPN, neurons that are critical for bilateral integration of cortical information and have been centrally implicated in autism spectrum disorders. It is my hope that the identification of molecular-genetic controls over CPN development will contribute to our understanding of neurodevelopmental disorders.

Key Recent Publications

  • MacDonald JL*, Fame RM*, Azim E, Shnider SJ, Molyneaux BJ, Arlotta P, and Macklis JD. “Specification of cortical projection neurons:transcriptional mechanisms.”
    Comprehensive Developmental Neuroscience Encyclopdia. Rubenstein J, Rakic P, eds. Elsevier. (in press). *Co-first authors
  • Fame RM*, MacDonald, JL*, and Macklis, JD. 2011 “Development, Specification, and Diversity of Callosal Projection Neurons.” Trends in Neurosciences. 34(1):41-50 *Co- first authors
  • Molyneaux, B.J.*, Arlotta, P.*, Fame, R.M. †, MacDonald, J.L. †, MacQuarrie, K.L., and Macklis, J.D. 2009 “Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons.” Journal of Neuroscience. 29(39):12343-54 (with cover) *Co-first authors; †Co-second authors

Previous Publications

  • MacDonald, J.L., Berndt, A., Verster, A., and Roskams, A.J. 2010 “MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons.” MCN. 44:55-67
  • MacDonald, J.L. and Roskams, A.J. 2009 “Epigenetic regulation of nervous system development by DNA methylation and histone deacetylation.” Progress in Neurobiology. 88(3):170-83
  • MacDonald, J.L. and Roskams, A.J. 2008. “Histone deacetylases 1 and 2 are expressed at distinct stages of neuro-glial development.” Developmental Dynamics 237(8):2256-67.
  • MacDonald, J.L., Gin, C.S., Roskams, A.J. 2005. “Stage-specific induction of DNA methyltransferases in olfactory receptor neuron development.” Developmental Biology 288(2):461-73.
  • Carter, L.A., MacDonald, J.L., Roskams, A.J. 2004. “Olfactory horizontal basal cells demonstrate a conserved multipotent progenitor phenotype.” Journal of Neuroscience 24(25):5670-83.

Hari Padmanabhan

HSCRB
Postdoctoral Fellow
Contact Info
hari_padmanabhan@harvard.edu

Hari Padmanabhan

Tata Institute of Fundamental Research, Ph.D.

During development, projection neurons of the cerebral cortex are generated first from the pallial ventricular zone followed by astrocytes and oligodendrocytes. Since the same population of progenitors give rise to both neurons and glia sequentially, there are switches that are flipped OFF after neurogensis and new switches turned ON to initiate proper gliogenesis. Moreover, during the phase of neurogenesis, spatially restricted transcriptional programs regulate the generation of broad classes of neurons like long distance projection neurons and interneurons from dorsal and ventral ventricular zone, respectively. We are interested in understanding how these are achieved in a precise manner. This project is in collaboration with Eiman Azim, a former graduate student in the lab, and Chris Devine, who is an undegraduate student.

The generation of induced pluripotent cells has demonstarted that terminal differentiation of a cell type may not be an irreversible process. By knowing key molecular controls, it is possible to revert differentiated cells to an immature state and then redirect them along an alternate differentiation pathway. Similarly, differentiated cells can also potentially be directly reprogrammed to other cell types. By understanding the genetic mechanisms that regulate orderely neurogenesis and gliogenesis, we hope to coax cells to switch from one stable state to another. This project is in collaboration with Kadir Ozkan, graduate student in the lab.

Prior to joining the Macklis Lab in October, 2008, I did my PhD at the Tata Institute of Fundamental Research, India. During my thesis research, I studied the role of LIM-domain containing transcription factors and their cofactors in neuronal development in fruit flies and mice.

Key Recent Publications:

  • Custo Greig LF*, Woodworth MB*, Galazo MJ†, Padmanabhan HK†, Macklis JD. Molecular logic of neocortical projection neuron specification and development. Nature Reviews Neuroscience. (*co-first authors, †equally contributing second authors). In Press.
  • Cederquist GY, Azim E, Shnider SJ, Padmanabhan H, Macklis JD. Lmo4 establishes rostral motor cortex projection neuron subtype diversity. J Neurosci. 2013 Apr 10;33(15):6321-32.
  • Sohur US, Padmanabhan HK, Kotchetkov IS, Menezes JR, Macklis JD. Anatomic and Molecular Development of Corticostriatal Projection Neurons in Mice. Cereb Cortex. 2012 Oct 31.

Previous Publications

  • Lakshmi Subramanian, Anindita Sarkar, Ashwin S. Shetty, Bhavana Muralidharan, Hari Padmanabhan, Michael Piper, Edwin S. Monuki, Ingolf Bach, Richard M. Gronostajski, Linda J. Richards, Shubha Tole. Transcription factor Lhx2 is necessary and sufficient to suppress astrogliogenesis and promote neurogenesis in the developing hippocampus PNAS (2011) 108(27) E265–E274.
  • Padmanabhan H., Mugdha Deshpande, Neha Sharma, Neha Rajadhyaksha, Nitya Ramkumar, Kenichi Kimura, Veronica Rodrigues, Shubha Tole. Chip is required for post eclosion behavior in Drosophila. J. Neurosci. (2008) 28(37) 9145-50.
  • Ryan Remedios, Dhananjay Huilgol, Bhaskar Saha, Padmanabhan Hari, Lahar Bhatnagar, Toshio Ohshima, Anastassia Stoykova and Shubha Tole. A novel stream of amygdaloid cells from the caudal telencephalon reveals a developmental link between the amygdala and the neocortex. Nat. Neurosci. (2007) 10(9)1141-50.
  • Bhaskar Saha, Padmanabhan Hari, Dhananjay Huilgol and Shubha Tole. Dual Role for LIM-HD Gene Lhx2 in the Formation of the Lateral Olfactory Tract. J. Neurosci. (2007) 27(9) 2290-2297
  • Lakshmi Subramanian, Vanisha Lakhina, Hari Padmanabhan and Shubha Tole. Role of LIM-HD Genes in the Specification of Cell Identity. Proc. Indian Natn Sci Acad. (2003) B69 No. 5 pp 803-824.
  • Amrita Gupta, P. Hari Kumar, T.K. Dineshkumar, Umesh Varshney and Hosahalli S. Subramanya. Crystal structure of Rv2118c: An AdoMet-dependent Methyltransferase from Mycobacterium tuberculosis H37Rv. J. Mol. Biol. (2001) 312, 381-391

Alexandros Poulopoulos

HSCRB
Postdoctoral Fellow
Contact Info
alexandros_poulopoulos@harvard.edu

Alexandros Poulopoulos

University of Göttingen, Ph.D.

I joined the Macklis lab in May 2010, interested in how cortical circuits form. Drawing from diverse backgrounds, colleagues in the lab and I combine methodologies with the aim of identifying novel mechanisms that instruct growing axons as they navigate the complex environment of the developing brain. We employ transplantation, transgenesis, tracing, sorting, and proteomics in order to examine the dynamic cellular crosstalk and molecular interactions that guide neuronal processes to reach meaningful targets and form functional circuits.

Before coming to Boston, I worked on mechanisms of synaptogenesis in the lab of Nils Brose at the Max Planck Institute of Experimental Medicine, receiving a Ph.D. in Neuroscience from the University of Göttingen, Germany in 2008. As an undergrad, I studied Biology at the University of Athens, Greece, working in the lab of Spiros Efthimiopoulos on amyloid processing in dementia.

  • Soykan T, Schneeberger D, Tria G, Buechner C, Bader N, Svergun D, Tessmer I, Poulopoulos A, Papadopoulos T, Varoqueaux F, Schindelin H, Brose N. A conformational switch in collybistin determines the differentiation of inhibitory postsynapses. EMBO J. 33(18):2113-33 (2014).
  • Poulopoulos A*, Soykan T*, Tuffy LP, Hammer M, Varoqueaux F, Brose N. Homodimerization and isoform-specific heterodimerization of neuroligins. Biochem J. 446(2):321-30 (2012).
  • Jedlicka P, Hoon M, Papadopoulos T, Vlachos A, Winkels R, Poulopoulos A, Betz H, Deller T, Brose N, Varoqueaux F, Schwarzacher SW. Increased dentate gyrus excitability in neuroligin-2-deficient mice in vivo. Cereb Cortex. 21(2):357-67 (2011). 
  • Poulopoulos A. 'Holistic' synaptogenesis. Biochem Soc Trans. 38(2):511-5 (2010). 
  • Poulopoulos A*, Aramuni G*, Meyer G, Soykan T, Hoon M, Papadopoulos T, Zhang M, Paarmann I, Fuchs C, Harvey K, Jedlicka P, Schwarzacher SW, Betz H, Harvey RJ, Brose N, Zhang W, Varoqueaux F. Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin. Neuron. 63(5):628-42 (2009). 
  • Fotinopoulou A, Tsachaki M, Vlavaki M, Poulopoulos A, Rostagno A, Frangione B, Ghiso J, Efthimiopoulos S. BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid beta (Abeta) production. J Biol Chem.280(35):30768-72 (2005). 
  • Poulopoulou C, Markakis I, Davaki P, Nikolaou C, Poulopoulos A, Raptis E, Vassilopoulos D. Modulation of voltage-gated potassium channels in human T lymphocytes by extracellular glutamate. Mol Pharmacol. 67(3):856-67 (2005).

Vibhu Sahni

HSCRB
Postdoctoral Fellow
Contact Info
vibhu_sahni@harvard.edu

Vibhu Sahni

Northwestern University, Ph.D.

email: vibhu_sahni [at] harvard [dot] edu

I joined the Macklis lab in September 2009 as a postdoctoral fellow. I am interested in the investigation of the developmental mechanisms in the nervous system and their application in understanding disease process as well as the development of therapeutic strategies for nervous system repair. In the Macklis lab, I am focusing on the development of corticospinal motor neurons (CSMN) in two broad areas: (1) Functional characterization of genes identified by two former members of the lab, Denis Jabaudon and Sara Shnider, as candidates for controlling CSMN subtype-specific development and segmental target specificity. In this study, I am combining both gain- and loss-of-function analyses in CSMN subtypes to examine the roles of these candidate control genes on segmental targeting in the spinal cord. (2) Development of strategies to apply our existing knowledge of CSMN development, that was previously identified in the lab, toward CSMN regeneration after spinal cord injury.

Prior to arriving at the Macklis lab, I completed a Ph.D. in Neuroscience at Northwestern University. During my thesis work under the guidance of Prof. John A. Kessler, I worked on the mechanisms of astrocytic development and investigated their role in astrogliosis and functional recovery after spinal cord injury in the mouse. I completed my undergraduate studies at the University of Mumbai, India.

Previous Publications

  • Tysseling VM, Mithal D, Sahni V, Birch D, Jung H, Miller RJ, Kessler JA. “SDF1 in the dorsal corticospinal tract promotes CXCR4+ cell migration after spinal cord injury.” J Neuroinflammation. 2011 Feb 16;8(1):16.
  • Sahni V, Kessler JA. “Stem cell therapies for spinal cord injury.” Nat Rev Neurol. 2010 Jul;6(7):363-72.
  • Tysseling VM*, Sahni V*, Pashuck ET, Birch D, Hebert A, Czeisler C, Stupp SI, Kessler JA. “Self-assembling peptide amphiphile promotes plasticity of serotonergic fibers following spinal cord injury.” J Neurosci Res. 2010 Nov 1;88(14):3161-70. (*Both authors contributed equally to this work)
  • Sahni V, Mukhopadhyay A, Tysseling VM, Birch D, Hebert A, Mcguire TL, Stupp S and Kessler JA. BMPR1a and BMPR1b receptor signaling exert opposing effects on astrogliosis after spinal cord injury. J Neurosci. Feb; 30: 1839-1855 (2010).
  • Tysseling VM*, Sahni V*, Niece KL, Birch D, Czeisler C, Fehlings MG, Stupp S, and Kessler JA. Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury.” J Neurosci. Apr 2;28(14):3814-23 (2008). (* Both authors contributed equally to this work)
  • Niece KL, Czeisler C, Sahni V, Tysseling VM, Pashuck ET, Kessler JA and Stupp S. Modification of gelation kinetics in bioactive peptide amphiphiles. Biomaterials. Dec;29(34):4501-9 (2008).
  • Kan L, Israsena N, Zhang Z, Hu M, Zhao LR, Jalali A, Sahni V, Kessler JA. Sox1 acts through multiple independent pathways to promote neurogenesis. Dev. Biol. May 15;269(2):580-94 (2004).
  • Goings GE, Sahni V, Szele FG. Migration patterns of subventricular zone cells in adult mice change after cerebral cortex injury. Brain Res. Jan 23;996(2):213-26 (2004).

Seth Shipman

HSCRB
Postdoctoral Fellow
Contact Info
seth_shipman@harvard.edu

Shipman SL, Nicoll RA. (2012). A subtype-specific function for the extracellular domain of neuroligin 1 in hippocampal LTP. Neuron; 76(2): 309-16.

Shipman SL, Nicoll RA. (2012). Dimerization of postsynaptic neuroligin drives synaptic assembly via transsynaptic clustering of neurexin. PNAS; 109(47): 19432-7.

Shipman SL, Schnell E, Hirai T, Chen BS, Roche KW, Nicoll RA. (2011). Functional dependence of neuroligin on a new non-PDZ intracellular domain. Nature Neuroscience; 14(6):718-26.

Shipman SL, Baker EK, Pearlson GD, Astur RS. (2009). Absence of established sex differences in patients with schizophrenia on a 2-dimensional object array task. Psychiatry Research; 166(2-3): 158-65.

Shipman SL, Astur RS (2008). Factors Affecting the Hippocampal BOLD Response During fMRI: Activation versus Deactivation. Behavioral Brain Research; 187(2): 433-41.

Yasuhiro Itoh

HSCRB
Postdoctoral Fellow
Contact Info
yasuhiro_ito@harvard.edu
Ioana Florea

Ioana Florea

HSCRB
Laboratory Technician
Contact Info
ioana_florea@harvard.edu
Ryan H.

Ryan H.

HSCRB
Laboratory Technician
Ryan Lindeborg

Ryan Lindeborg

HSCRB
Undergraduate '16

I joined the lab in the winter of 2013 as an undergraduate at Harvard College.  I am currently working with Zhaoying Xu, a PhD candidate in the Program in Neuroscience at Harvard, to identify molecular controls over the lineage- and subtype-specific development of corticostriatal projection neurons (CStrPN), including fate specification, maturation, and connectivity.  Understanding molecular developmental controls for CStrPN might contribute toward elucidating their selective vulnerability in Huntington’s disease and toward induction of endogenous progenitors to differentiate into functional CStrPN and integrate into functional corticostriatal circuitry.

My previous research experience includes working on the optimization of platinum nanoparticles for proton exchange membrane fuel cells using pulse electrochemical deposition under Dr. Steve Buratto at University of California, Santa Barbara.  I also investigated the effect of both surface modification of poly(methyl methacrylate) scaffolds through plasma etching and different media on the migration of fibroblasts under Dr. Miriam Rafailovich at the State University of New York at Stonybrook.

Frances Ding

Frances Ding

HSCRB
Undergraduate '17

I joined the lab in the spring of 2014, and  I am currently working with Vibhu Sahni, a postdoctoral fellow, to identify and characterize molecular controls over the subtype-specific development of corticospinal motor neurons (CSMN) which form the corticospinal tract controlling voluntary movement.  Understanding molecular developmental controls for CSMN might contribute toward elucidating their vulnerability in motor neuron diseases, most prominently amyotrophic lateral sclerosis (ALS), and in spinal cord injury. Further understanding of CSMN developmental controls may also contribute to future strategies for repair and regeneration of CSMN and re-establishment of neural circuitry.

Previously, I have had research experience studying the autosomal recessive disease, Smith-Lemli-Opitz Syndrome (SLOS). The disease involves impaired cholesterol synthesis, which causes cell death particularly in the brain, due to a lack of cholesterol and a build-up of toxic cholesterol precursors. SLOS results in phenotypes ranging from mild intellectual disability to lethal malformations. I worked under Dr. Zeljka Korade at Vanderbilt University to analyze serotonin levels in mice models for SLOS and also investigate the potential therapeutic effects of antioxidants on neuronal survival in SLOS cell lines.

Michelle Guo

Michelle Guo

HSCRB
Undergraduate '17

I joined the lab in winter of 2014. I work with Alex Poulopoulos, a postdoc in the lab, to study the role of transient circuitry in the formation of mature circuits. I aim to identify candidate transient, developmentally relevant, synaptic connections between specific neuron subtypes. Ultimately, I would like to functionally examine the potential role of these synaptic connections in the development of mature cortical circuits. These initial findings will guide the design of experiments to interrupt synaptic activity in order to identify the potential developmental role of these transient synapses. In this way I hope to contribute to our understanding of the functions of these transient circuits in the formation of mature brain circuitry, to our appreciation for the sophisticated mechanisms that allow the healthy brain to connect, and to how we may best intervene when we need to repair damaged connections.

Before coming to Harvard, I conducted biomedical research in the lab of Donna Leonardi at the Bergen County Academies high school. I studied the role of resveratrol and metformin in a cellular model of Alzheimer’s disease. At the New Jersey Governor’s School in the Sciences, I had the opportunity to conduct a team chemistry research project on pseudo-zero-order kinetic systems. I also conducted stem cell research with Dr. George Daley of the Children’s Hospital of Boston. I performed electron microscopy to investigate the bioenergetics role of mitochondria in pluripotent stem cells.