Dominique Alfandari

Dominique Alfandari, Ph.D.

Professor of Developmental Biology

Office phone: 413-577-4269

Lab phone: 413-545-3739

Fax: 413-545-6326

Email: alfandar [at] vasci [dot] umass [dot] edu

Office location: 427B ISB

Mailing address:

661 North Pleasant Street
Amherst, Mass 01003

Alfandari lab website
Hélène Cousin, Co-Investigator
Alfandari stats
Molecular and Cellular Biology Graduate Program
Previous members of the lab

Movie is a model of ADAM13 protein. The Metalloprotease domain is grey, Disintegrin in Blue, Cystein rich in purple, EGF repeat in green.

Ph.D.: University of Pierre & Marie Curie, Paris 6 (France), 1994
Postdoctoral Training: University of Virginia, Department of Cell Biology 

Previous positions: Maitre de conference UPMC 1996-2000 (Tenure), Research Instructor UVA 2000-2003

Awards: Predoctoral fellowship MRT 1991-1994. Post doctoral fellowship FRM 1995-1996. NIH RO1DE14365 (2001-6),  NIH RO1DE16289 (2006-2023), NSF 0544015 (2005-08), NIH R24OD021485 (2017-2021), NIH RO1DE02634 (2018-2023 PI Moody, co-I Alfandari).

*Active grants are underlined.

Classes:

ANIMLSCI 390E - Fundamental Vertebrate Embryology

ANIMLSCI 697J - Cell, Genes and Development

ANIMLSCI 795A - Journal Club in Cells, Genes and Development

Craniofacial Development

The Alfandari lab studies how the face of vertebrate embryos is built. The main source of cells for this process are the Cranial Neural Crest Cells (CNC), which are induced at the border of the neural plate (Future brain and spinal chord) and move ventrally to produce the bones, cartilage, muscles and ganglia of the face. 

 

Happening now:

New RO1 with our collaboartor Dr. Sally Mody to study the role of Six1 partners in Craniofacial development and Branciootorenal spectrum disorder.

Renewal of our long term RO1 to study the mechanism of Cranial neural crest cell migration.

Also a New NIH grant to produce and characterize 100 monoclonal antibodies to Xenopus protein for the scientific community.

Our latest BIG paper published in E-Life shows how ADAM can regulate gene expression.

Alban Gaultier, an Alfandari lab Alumni now Assistant Professor at UVA made the news. Congrat Alban!!

We are recruiting:

         Project 1: To study the interaction between the transcription factor Arid3a and the ADAM metalloproteases

         Project 2: To identify partners of the transcription factor Six1 in Xenopus embryos

         Project 3: To produce and characterise monoclonal antibody. This project is excellent for students interested in industry rather than academia.

 

 The following movies show cranial neural crest cell migration in vivo (in the embryo) or in vitro (In a dish). In vivo the neural crest were labeled with a fluorescent marker before they were grafted into a host embryo.

 

 

How does a cell move? Cells move all the time in our bodies, to repair wounds, to attack pathogens, to fight cancer or in some cases to allow cancer to spread and invade new organs. In embryos, cells move great distances to produce the various shapes and complex organs.

We study how cells move in a developing embryo. More specifically, how do they start? How do they know where to go, where and when to stop? One of the best examples of cell movement (see movie) is the migration of cranial neural crest cells. They are borne at the border between the neural and non-neural ectoderm in the dorsal side of the embryo and migrate to the ventral side of the embryo to create all of the structures of the face (bones, cartilage, muscle and ganglia).

Our laboratory is funded by the NIH (NIDCR) to understand how metalloproteases that are expressed at the surface of the cranial neural crest help these cells move. We aim to understand which proteins are cut by these proteases and how this cleavage changes the function of these target proteins to favor cell movement. Clearly if these proteases can promote cell migration in the embryo, they may also promote cancer cell dispersion (Metastasis) so that understanding how they work and how we can stop their function may also lead to new approaches to cancer treatment.

The Alfandari lab in the news.

Previous members of the lab

 

Dutta K, Bochicchio D, Ribbe AE, Alfandari D, Mager J, Pavan GM, Thayumanavan S.  2019.  Symbiotic Self-Assembly Strategy toward Lipid-Encased Cross-Linked Polymer Nanoparticles for Efficient Gene Silencing. ACS Applied Materials & Interfaces. 11:24971–24983.
Cousin H, Alfandari D.  2018.  Cranial Neural Crest Explants. Cold Spring Harbor Protocols. 2018:pdb.prot097394.
Wells AC, Daniels KA, Angelou CC, Fagerberg E, Burnside AS, Markstein M, Alfandari D, Welsh RM, Pobezinskaya EL, Pobezinsky LA.  2017.  Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells. eLife. 6
Khedgikar V, Abbruzzese G, Mathavan K, Szydlo H, Cousin H, Alfandari D.  2017.  Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2alpha and arid3a.. {eLife}. 6
Neilson KM, Abbruzzesse G, Kenyon K, Bartolo V, Krohn P, Alfandari D, Moody SA.  2017.  Pa2G4 is a novel Six1 co-factor that is required for neural crest and otic development. Developmental Biology. 421:171–182.
Abbruzzese G, Becker SF, Kashef J, Alfandari D.  2016.  ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site. Developmental Biology. 415:383–390.
Langhe RP, Gudzenko T, Bachmann M, Becker SF, Gonnermann C, Winter C, Abbruzzese G, Alfandari D, Kratzer M-C, Franz CM et al..  2016.  Cadherin-11 localizes to focal adhesions and promotes cell–substrate adhesion. Nature Communications. 7:10909.
Bajanca F, Alfandari D, Thorsteinsdóttir S, Théveneau E.  2015.  Editorial: Cell adhesion in development.. Dev Biol. 401(1):1.
Abbruzzese G, Gorny A-K, Kaufmann LT, Cousin H, Kleino I, Steinbeisser H, Alfandari D.  2015.  The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity.. J Cell Sci. 128(6):1139-49.
Moody SA, Neilson KM, Kenyon KL, Alfandari D, Pignoni F.  2015.  Using Xenopus to discover new genes involved in Branchiootorenal spectrum disorders.. Comp Biochem Physiol C Toxicol Pharmacol.
Abbruzzese G, Becker SF, Kashef J, Alfandari D.  2015.  ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.. Dev Biol.
Moody SA, Neilson KM, Kenyon KL, Alfandari D, Pignoni F.  2015.  Using Xenopus to discover new genes involved in branchiootorenal spectrum disorders. Comparative Biochemistry and Physiology Part C: Toxicology {&} Pharmacology. 178:16–24.
Abbruzzese G, Cousin H, Salicioni AM, Alfandari D.  2014.  GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration.. Mol Biol Cell.
Cousin H, Abbruzzese G, McCusker C, Alfandari D.  2012.  ADAM13 function is required in the 3 dimensional context of the embryo during cranial neural crest cell migration in Xenopus laevis.. Developmental biology.
Wang L, Pawlak E, Johnson PJ, Belknap JK, Alfandari D, Black SJ.  2012.  Effects of cleavage by a disintegrin and metalloproteinase with thrombospondin motifs-4 on gene expression and protein content of versican and aggrecan in the digital laminae of horses with starch gruel-induced laminitis.. American journal of veterinary research. 73(7):1047-56.
Pawlak E, Wang L, Johnson PJ, Nuovo G, Taye A, Belknap JK, Alfandari D, Black SJ.  2012.  Distribution and processing of a disintegrin and metalloproteinase with thrombospondin motifs-4, aggrecan, versican, and hyaluronan in equine digital laminae.. American journal of veterinary research. 73(7):1035-46.
Cousin H, Alfandari D.  2011.  ADAM and cell migration: the unexpected role of the cytoplasmic domain. Médecine sciences : M/S. 27(12):1069-71.
Cousin H, Abbruzzese G, Kerdavid E, Gaultier A, Alfandari D.  2011.  Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain8-a expression and cranial neural crest cell migration.. Developmental cell. 20(2):256-63.
Alfandari D, Cousin H, Marsden M.  2010.  Mechanism of Xenopus cranial neural crest cell migration.. Cell adhesion & migration. 4(4):553-60.
McCusker C, Cousin H, Neuner R, Alfandari D.  2009.  Extracellular cleavage of cadherin-11 by ADAM metalloproteases is essential for Xenopus cranial neural crest cell migration.. Molecular biology of the cell. 20(1):78-89.
Neuner R, Cousin H, McCusker C, Coyne M, Alfandari D.  2009.  Xenopus ADAM19 is involved in neural, neural crest and muscle development.. Mechanisms of development. 126(3-4):240-55.
McCusker CD, Alfandari D.  2009.  Life after proteolysis: Exploring the signaling capabilities of classical cadherin cleavage fragments.. Communicative & integrative biology. 2(2):155-7.
Coyne MJ, Cousin H, Loftus JP, Johnson PJ, Belknap JK, Gradil CM, Black SJ, Alfandari D.  2009.  Cloning and expression of ADAM-related metalloproteases in equine laminitis.. Veterinary immunology and immunopathology. 129(3-4):231-41.
Alfandari D, McCusker C, Cousin H.  2009.  ADAM function in embryogenesis.. Seminars in cell & developmental biology. 20(2):153-63.
Cousin H, Desimone DW, Alfandari D.  2008.  PACSIN2 regulates cell adhesion during gastrulation in Xenopus laevis.. Developmental biology. 319(1):86-99.
Ito J, Yoon S-Y, Lee B, Vanderheyden V, Vermassen E, Wojcikiewicz R, Alfandari D, De Smedt H, Parys JB, Fissore RA.  2008.  Inositol 1,4,5-trisphosphate receptor 1, a widespread Ca2+ channel, is a novel substrate of polo-like kinase 1 in eggs.. Developmental biology. 320(2):402-13.
Kurokawa M, Yoon SY, Alfandari D, Fukami K, Sato K-ichi, Fissore RA.  2007.  Proteolytic processing of phospholipase Czeta and [Ca2+]i oscillations during mammalian fertilization.. Developmental biology. 312(1):407-18.
Lee B, Vermassen E, Yoon S-Y, Vanderheyden V, Ito J, Alfandari D, De Smedt H, Parys JB, Fissore RA.  2006.  Phosphorylation of IP3R1 and the regulation of [Ca2+]i responses at fertilization: a role for the MAP kinase pathway.. Development (Cambridge, England). 133(21):4355-65.
Cousin H, Alfandari D.  2004.  A PTP-PEST-like protein affects alpha5beta1-integrin-dependent matrix assembly, cell adhesion, and migration in Xenopus gastrula.. Developmental biology. 265(2):416-32.
Cousin H, Gaultier A, Bleux C, Darribère T, Alfandari D.  2000.  PACSIN2 is a regulator of the metalloprotease/disintegrin ADAM13.. Developmental biology. 227(1):197-210.