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

Research Interests

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.

Here is the link to the most current list of antibodies and their target. https://docs.google.com/spreadsheets/d/1AFLp1PcfMkXJ8SVSZ6W-HaE0K5pC1nZ6WlnUqzY_Zu0/edit?usp=sharing

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

Lab Personnel

Name	Email	Phone	Office
Pandey, Ankit Graduate Student - ABBS	ankitpandey [at] umass.edu	413-545-3739	ISB 455

Publications

Narayanaswamy, V., Pentecost, B. T., Schoen, C. N., Alfandari, D., Schneider, S. S., Baker, R., & Arcaro, K. F.. (2022). Neutralizing Antibodies and Cytokines in Breast Milk After Coronavirus Disease 2019 (COVID-19) mRNA Vaccination. Obstet Gynecol, 139(2), 181-191. presented at the 2022 02 01. doi:10.1097/AOG.0000000000004661

Keer, S., Cousin, H., Jourdeuil, K., Neilson, K. M., Tavares, A. L. P., Alfandari, D., & Moody, S. A.. (2022). Mcrs1 is required for branchial arch and cranial cartilage development. Dev Biol, 489, 62-75. presented at the 2022 09. doi:10.1016/j.ydbio.2022.06.002

Narayanaswamy, V., Pentecost, B. T., Telfer, J. C., Burnside, A. S., Schneider, S. S., Alfandari, D., et al.. (2022). Durable antibody and effector memory T cell responses in breastmilk from women with SARS-CoV-2. Front Immunol, 13, 985226. presented at the 2022. doi:10.3389/fimmu.2022.985226

Narayanaswamy, V., Pentecost, B., Alfandari, D., Chin, E., Minor, K., Kastrinakis, A., et al.. (2021). Humoral and Cell-Mediated Immune Response in Colostrum from Women Diagnosed Positive for SARS-CoV-2. Breastfeed Med, 16(12), 987-994. presented at the 2021 12. doi:10.1089/bfm.2021.0082

Neilson, K. M., Keer, S., Bousquet, N., Macrorie, O., Majumdar, H. D., Kenyon, K. L., et al.. (2020). Mcrs1 interacts with Six1 to influence early craniofacial and otic development. Developmental Biology, 467, 39–50. Retrieved from https://doi.org/10.1016/j.ydbio.2020.08.013

Andrieu, C., Montigny, A., Bibonne, A., Despin-Guitard, E., Alfandari, D., & Théveneau, E.. (2020). MMP14 is required for delamination of chick neural crest cells independently of its catalytic activity. Development, 147, dev183954. Retrieved from https://doi.org/10.1242/dev.183954

Dutta, K., Bochicchio, D., Ribbe, A. E., Alfandari, D., Mager, J., Pavan, G. M., & 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. Retrieved from https://doi.org/10.1021/acsami.9b04731

Cousin, H., & Alfandari, D.. (2018). Cranial Neural Crest Explants. Cold Spring Harbor Protocols, 2018, pdb.prot097394. Retrieved from https://doi.org/10.1101/pdb.prot097394

Alfandari, D., & Taneyhill, L. A.. (2018). Cut loose and run: The complex role of ADAM proteases during neural crest cell development. genesis, 56, e23095. Retrieved from https://doi.org/10.1002/dvg.23095

Li, J., Perfetto, M., Neuner, R., Bahudhanapati, H., Christian, L., Mathavan, K., et al.. (2018). XenopusADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13. Development, 145, dev158154. Retrieved from https://doi.org/10.1242/dev.158154

Neilson, K. M., Abbruzzesse, G., Kenyon, K., Bartolo, V., Krohn, P., Alfandari, D., & Moody, S. A.. (2017). Pa2G4 is a novel Six1 co-factor that is required for neural crest and otic development. Developmental Biology, 421, 171–182. presented at the jan. Retrieved from https://doi.org/10.1016/j.ydbio.2016.11.021

Serrano, B. P., Szydlo, H. S., Alfandari, D., & Hardy, J. A.. (2017). Active site–adjacent phosphorylation at Tyr-397 by c-Abl kinase inactivates caspase-9. Journal of Biological Chemistry, 292, 21352–21365. Retrieved from https://doi.org/10.1074/jbc.m117.811976

Mathavan, K., Khedgikar, V., Bartolo, V., & Alfandari, D.. (2017). The ectodomain of cadherin-11 binds to erbB2 and stimulates Akt phosphorylation to promote cranial neural crest cell migration. (A. Ahmad, Ed.){PLOS} {ONE}, 12, e0188963. Retrieved from https://doi.org/10.1371/journal.pone.0188963

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. presented at the aug. Retrieved from https://doi.org/10.7554/elife.26898

Wells, A. C., Daniels, K. A., Angelou, C. C., Fagerberg, E., Burnside, A. S., Markstein, M., et al.. (2017). Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells. eLife, 6. presented at the jul. Retrieved from https://doi.org/10.7554/elife.26398

Langhe, R. P., Gudzenko, T., Bachmann, M., Becker, S. F., Gonnermann, C., Winter, C., et al.. (2016). Cadherin-11 localizes to focal adhesions and promotes cell–substrate adhesion. Nature Communications, 7, 10909. presented at the mar. Retrieved from https://doi.org/10.1038/ncomms10909

Abbruzzese, G., Becker, S. F., Kashef, J., & Alfandari, D.. (2016). ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site. Developmental Biology, 415, 383–390. presented at the jul. Retrieved from https://doi.org/10.1016/j.ydbio.2015.07.018

Moody, S. A., Neilson, K. M., Kenyon, K. L., 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. presented at the dec. Retrieved from https://doi.org/10.1016/j.cbpc.2015.06.007

Bajanca, F., Alfandari, D., Thorsteinsdóttir, S., & Théveneau, E.. (2015). Editorial: Cell adhesion in development. Dev Biol, 401(1), 1. presented at the 2015 May 1.

Moody, S. A., Neilson, K. M., Kenyon, K. L., Alfandari, D., & Pignoni, F.. (2015). Using Xenopus to discover new genes involved in Branchiootorenal spectrum disorders. Comp Biochem Physiol C Toxicol Pharmacol. presented at the 2015 Jun 24.

Abbruzzese, G., Becker, S. F., Kashef, J., & Alfandari, D.. (2015). ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site. Dev Biol. presented at the 2015 Jul 21.

Abbruzzese, G., Gorny, A. - K., Kaufmann, L. T., 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. presented at the 2015 Mar 15.

Abbruzzese, G., Cousin, H., Salicioni, A. Maria, & Alfandari, D.. (2014). GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration. Mol Biol Cell. presented at the 2014 Oct 8.

Pawlak, E., Wang, L., Johnson, P. J., Nuovo, G., Taye, A., Belknap, J. K., et al.. (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. presented at the 2012 Jul.

Wang, L., Pawlak, E., Johnson, P. J., Belknap, J. K., Alfandari, D., & Black, S. J.. (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. presented at the 2012 Jul.

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. presented at the 2012 Jun 7.

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. presented at the 2011 Feb 15.

Cousin, H., & Alfandari, D.. (2011). ADAM and cell migration: the unexpected role of the cytoplasmic domain. Médecine sciences : M/S, 27(12), 1069-71. presented at the 2011 Dec.

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. presented at the 2009 Mar-Apr.

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. presented at the 2009 Jan.

Coyne, M. J., Cousin, H., Loftus, J. P., Johnson, P. J., Belknap, J. K., Gradil, C. M., et al.. (2009). Cloning and expression of ADAM-related metalloproteases in equine laminitis. Veterinary immunology and immunopathology, 129(3-4), 231-41. presented at the 2009 Jun 15.

Alfandari, D., McCusker, C., & Cousin, H.. (2009). ADAM function in embryogenesis. Seminars in cell & developmental biology, 20(2), 153-63. presented at the 2009 Apr.

McCusker, C. D., & Alfandari, D.. (2009). Life after proteolysis: Exploring the signaling capabilities of classical cadherin cleavage fragments. Communicative & integrative biology, 2(2), 155-7. presented at the 2009.

Ito, J., Yoon, S. - Y., Lee, B., Vanderheyden, V., Vermassen, E., Wojcikiewicz, R., et al.. (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. presented at the 2008 Aug 15.

Cousin, H., Desimone, D. W., & Alfandari, D.. (2008). PACSIN2 regulates cell adhesion during gastrulation in Xenopus laevis. Developmental biology, 319(1), 86-99. presented at the 2008 Jul 1.

Kurokawa, M., Yoon, S. Young, Alfandari, D., Fukami, K., Sato, K. -ichi, & Fissore, R. A.. (2007). Proteolytic processing of phospholipase Czeta and [Ca2+]i oscillations during mammalian fertilization. Developmental biology, 312(1), 407-18. presented at the 2007 Dec 1.

Lee, B., Vermassen, E., Yoon, S. - Y., Vanderheyden, V., Ito, J., Alfandari, D., et al.. (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. presented at the 2006 Nov.

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. presented at the 2004 Jan 15.

Former Lab Personnel

Name
Abbruzzese, Genevieve
Advani, Siddheshwari
Bibeau, Evan
Calabrese, John
Clarke, Katherine
Coyne, Michael
Gaultier, Alban
Grennon, Joseph
Horr, Brett
Kleino, Iivari
Kumar, Shiv
Loughman, Katie
Mathavan, Ketan
McCusker, Kate
McLinden, Gretchen
Neuner, Russell
Riedel, Rebecca
Splittstoesser, Daniel
Szydlo, Hannah
Taylor, Louis
Weir, Emma

Dominique Alfandari

Dominique Alfandari, Ph.D.