Dr. Arlotta received her Master’s in Biochemistry from the University of Trieste, Italy and her Ph.D. in Molecular Biology from the University of Portsmouth in the UK. She subsequently completed her postdoctoral training in Neuroscience at Harvard Medical School. In 2008, she became an Assistant Professor of Stem Cell and Regenerative Biology at Harvard University and is now an Associate Professor in the same department. Since 2007, she has been a principal Faculty Member at the Harvard Stem Cell Institute.
I am interested in understanding the molecular underpinnings that govern the birth, differentiation, and assembly into working circuitry of clinically relevant neuron types. The complexity of the nervous system fascinates me and I am moved to integrate developmental and evolutionary knowledge to inform novel strategies for circuit repair in the cerebral cortex.
Click here for a listing of Paola Arlotta's publications.
My general research interests include the development of the cerebral cortex and unravelling the molecular mechanisms behind the evolution of the brain in vertebrates, with the non-coding part of the genome as a central component of this process.
During my Wellcome Trust Four-Year PhD at the University of Manchester in Prof Nancy Papalopulu’s lab, I became interested in the role of non-coding RNAs in neural development. I focused on one brain-specific microRNA, called miR-9 and showed that it promotes neural progenitor heterogeneity both spatial and temporal, depending on the context. In addition to this, miR-9 regulates the extension and branching of cortical axons. For this work, I won the prestigious Beddington medal in 2012, awarded by the British Society for Developmental Biology for the best PhD thesis in the UK.
I recently joined the Arlotta lab to study the role of long non-coding RNAs during mammalian cortical development. In collaboration with John Rinn, my research goal is to uncover novel functions for this type of RNA during in the differentiation, migration and specification of cortical neurons.
Bonev B., Stanley P., Papalopulu, N. microRNA-9 modulates Hes1 ultradian oscillations by forming a negative feedback loop. (Cell Reports – in press)
Dajas-Bailador F., Bonev B., Garcez, P. Stanley P., Guillemot, F., Papalopulu N. (2012). microRNA-9 regulates axon extension and branching by targeting Map1b in mouse cortical neurons. Nature Neuroscience
Bonev, B., Pisco, A., and Papalopulu, N. (2011). MicroRNA-9 Reveals Regional Diversity of Neural Progenitors along the Anterior-Posterior Axis. Dev Cell 20, 19-32.
Love, N. R., Chen, Y., Bonev, B., Gilchrist, M. J., Fairclough, L., Lea, R., Mohun, T. J., Paredes, R., Zeef, L. A., and Amaya, E. (2011). Genome-wide analysis of gene expression during Xenopus tropicalis tadpole tail regeneration. BMC Dev Biol 11, 70.
Roth, M., Bonev, B., Lindsay, J., Lea, R., Panagiotaki, N., Houart, C. and Papalopulu, N. (2010). FoxG1 and TLE2 act cooperatively to regulate ventral telencephalon formation. Development 137, 1553-62.
I joined the Arlotta lab in the fall 2007 as a visiting PhD student at the European School of Molecular Biology (SEMM) in Naples where I was studying the intrinsic mechanisms that during development specify different types of inhibitory cortical interneurons during development. In the Arlotta lab I became interested in understanding the cellular and molecular mechanisms that control the interaction between excitatory projection neurons and inhibitory interneurons and which therefore control the establishment of functional circuitry in the mammalian cerebral cortex. I successfully defended my PhD thesis in 2011.
I received my Master’s degree in Biology from the University of Naples in 2004 and as an undergraduate I studied the role of the transcription factor COUP-TFI in the specification and migration of cortical interneurons in Michele Studer's lab at TIGEM, in Naples.
Molyneaux, B.J.*, Arlotta, P.*, MacQuarrie, K., and Macklis, J.D. (2009) Novel Subtype-specific Genes Identify Distinct Subpopulations of Callosal Projection Neurons. Journal of Neuroscience. 29:12343-54. (*equal contributions; with cover)
Joshi, P.S., Molyneaux, B.J., Feng, L., Xie, X., Macklis, J.D., and Gan, L. (2008) Bhlhb5 regulates the postmitotic acquisition of area identities in layers II-V of the developing neocortex. Neuron. 60:258-72.
Lai, T., Jabaudon, D., Molyneaux, B.J.*, Azim, E.,*, Arlotta, P., Menezes, J.R., and Macklis J.D. (2008) SOX5 Controls the Sequential Generation of Distinct Corticofugal Neuron Subtypes. Neuron. 57:232-247.
Arlotta, P.*, Molyneaux, B.J.*, Jabaudon, D., Yoshida, Y., and Macklis, J.D. (2008) Ctip2 controls the differentiation of medium spiny neurons and the establishment of the cellular architecture of the striatum. Journal of Neuroscience. 28:622-632.
Molyneaux, B.J.*, Arlotta, P.*, Menezes, J., and Macklis, J.D. (2007) Neuronal Subtype Specification in the Cerebral Cortex. Nature Reviews Neuroscience. 8:427-437.
Molyneaux, B.J.*, Arlotta, P.*, Hirata, T., Hibi, M., and Macklis, J.D. (2005) Fezl Is Required for the Birth and Specification of Corticospinal Motor Neurons. Neuron. 47: 817-831.
Arlotta, P.*, Molyneaux, B.J.*, Chen, J., Inoue, J., Kominami, R., and Macklis, J.D. (2005) Neuronal Subtype Specific Genes that Control Corticospinal Motor Neuron Development in vivo. Neuron. 45: 207-21 (with Preview and cover).
Molyneaux, B.J. and Hasselmo, M.E. (2002) GABA(B) presynaptic inhibition has an in vivo time constant sufficiently rapid to allow modulation at theta frequency. Journal of Neurophysiology. 87:1196-205.
Molyneaux, B.J., Mulcahey M.K., Stafford P., Langford G.M. (2000) Sequence and phylogenetic analysis of squid myosin-V: A vesicle motor in nerve cells. Cell Motility and the Cytoskeleton. 46:108-15.
Langford, G.M., and Molyneaux, B.J. (1998) Myosin V in the Brain: Mutations Lead to Neurological Defects. Brain Research Reviews. 28: 1-8.
Tabb, J.S, Molyneaux, B.J., Cohen, D.L., Kuznetsov, S.A., Langford, G.M. (1998) Myosin V Transports ER Vesicles in Axons. Journal of Cell Science. 111: 3221-3234.
Molyneaux, B.J., and Langford, G.M. (1997) Characterization of Antibodies to the Head and Tail Domains of Squid Brain Myosin V. Biological Bulletin. 193: 222-223.
I joined the lab in the fall 2009 for my second postdoc. Previously, I worked at the Italian Telethon institute (TIGEM) where I first approached the study of the cerebral cortex development. I studied the molecular mechanisms controlling the early areal patterning of the cortex in the embryo and I slowly became fascinated by the many neuronal and non neuronal cell types that can emerge from a relative simple and apparently uniform layer of progenitor cells. This is indeed THE fundamental question behind all studies of developmental biology: how does nature achieve complexity? That is, what are the signals that allow the incredible journey that culminates with a living organism and where are they, both in time and in space?
The cerebral cortex is perhaps one of the most complex structures of the entire CNS and it stands as a continuous challenge for us with all its layers, areas, neuronal subtypes[PA9] and afferent and efferent connections. One aspect that is slowly emerging is that different cell types may “collaborate” in order to generate the intrinsic puzzle that makes the adult cortex. In particular, I am personally interested in understanding the neuron to glia relation; I am trying to understand if and how different neurons of the cortex affect the differentiation and final maturation of the oligodendrocytes (the myelin-forming cells), what the signals are and, eventually, if it would be possible to use those signals to make new myelin.
I hope my studies will help to shed new light on fundamental biological questions and perhaps will further the development of new strategies to treat pathological states associated with myelin loss or damage like Multiple Sclerosis or Canavan disease.
I graduated in Biotechnology at University of Salento and did my thesis work on the role of Rac3 in the CNS, under the supervision of Dr. Ivan De Curtis at San Raffele, Milano. During my Ph.D at University of Genoa, under the guidance of Dr. Marco Canossa, I investigated the role of neurotrophin receptors on the axonal specification and the integration of newborn neurons during development and adult neurogenesis.
I joined the Arlotta lab as a graduate student in the summer of 2011, and after graduation in April 2012, I started work as a postdoctoral fellow. I am interested in the investigation of the role of a particular transcription factor critical for the development of corticospinal motor neurons.
I joined the Arlotta lab in the fall of 2009 as a Ph.D. student in the Biological and Biomedical Sciences program at the Harvard Graduate School of Arts and Sciences. I am interested in studying the cellular and molecular mechanisms that govern the differentiation of corticospinal motor neurons (CSMN) in the cerebral cortex. Besides this, I am interested in manipulating these key cell-intrinsic signals in vitro to direct mouse induced pluripotent stem cells to differentiate into corticofugal projection neurons, including CSMN. I hope that my work will aid in future cellular repair strategies to replace this particular neuronal subtype that specifically degenerates in Amyotrophic Lateral Sclerosis and is damaged in Spinal Cord Injury.
I completed my undergraduate studies at Cornell University, and graduated with a B.A. Magna cum Laude, in Molecular and Cell Biology with a minor in Japanese. While at Cornell, I worked with Professor Volker Vogt on devising an in vitro assembly system for Simian Immunodeficiency Virus Gag. For my undergraduate and graduate studies, I have been awarded the National Science Scholarship (BS and PhD) by the Agency for Science, Technology and Research from Singapore.
I joined the Arlotta lab in the spring of 2012 as a graduate student in the Department of Molecular and Cellular Biology. My research interests focus in the epigenetics of neuronal development. I am currently working on direct reprogramming and transdifferentiation of cortical neurons. Additionally, I am interested in science policy development with respect to stem cells.
Before beginning my studies at Harvard, I received my B.S. in Biotechnology and Bioinformatics and a minor in Science, Technology and Society from the Rochester Institute of Technology. There I worked in Dina Newman’s lab, where I studied the role of the PYCS gene in Presbycusis (age-related hearing-loss). I have also worked for Robert Dirksen at the University of Rochester, studying allele-specific gene silencing in autosomal dominant skeletal myopathies, such as Central Core Disease and Malignant Hyperthermia. Additionally, I have worked for Roger Tsien at the University of California San Diego, in the development of dual modality imaging probes that combine fluorescence with Positron Emission Tomography (PET) technologies.
Loy RE, Mostajo-Radji MA, Lueck JD, Dirksen RT. Allele Specific Gene Silencing in Autosomal-Dominant Skeletal Myopathies. Biophysical Journal 98 (3) 712a-713a