Dr. McLane's research
2004-2005: front row: Claire Zelinskas
Tian (PhD graduate student), Apoorva
Srivastava ('05), back row: Xiaoming Zhang (research specialist), Carrie
Paquette-Straub (research associate, along with her soon-to-be born Rachel!),
Dr. McLane, Bryn
2005-2006: front row: as in 2004-2005, with the addition of Dara Missan
('06, back row, far right) and Brett Hensley
('07, front far right). Collaborator Dr. Mary Beth Miele is next to Dr. McLane
in the front row.
2006-2007: Stephanie DiRosato ('08), Carrie Paquette-Straub, Dr. McLane, Jing Tian2010-2011: clockwise from front left: Dr. McLane, Sarah Greenwood ('12), Stefan Hailey (MS grad student), Ryan Penn ('12), Brendan Mooney ('12)
Cancer metastasis is the major obstacle to cancer cure. Melanoma is one of the most rapidly increasing types of cancer, and malignant melanoma is particularly aggressive in its ability to metastasize and the lack of any successful treatment. In 1990, I started working with a group of naturally occurring protein from viper venom, called DISINTEGRINS. Some of these proteins can be injected into a mouse along with melanoma cells and prevent the tumor cells from forming new colonies within the lungs.
The snake pictured above is Eristocophis macmahoni, which originates
from the deserts of southwestern Asian, and which produces a very unique
disintegrin, called eristostatin. This
disintegrin can inhibit melanoma cell lung colonization in a mouse model. The
mechanism by which it accomplishes this is still unknown. My research is looking
into the motifs within eristostatin's sequence which gives it the ability to
have this anti-cancer property. Undergraduate students (Alice Wong '03, Melissa
Kuchar '01) in my lab described the receptors found on the surface of four
different types of melanoma cells1, and the effect of using mutated
forms of eristostatin in interactions with those melanoma cells2. Claire
Zelinskas ('05) and Apoorva Srivastava ('05) created a series of alanine
mutations within eristostatin's sequence and expressed these mutations as
recombinant fusion proteins. Bryn Werbos ('05) investigated how
we can improve the recombinant protein yield by purifying inclusion
bodies. Jing Tian's graduate studies focused on characterizing
the recombinant proteins' interactions with 1205-LU, C8161, M24met and MV3
melanoma cells using confocal microscopy, flow cytometry and in vivo
hematogenous metastasis. In addition, she investigated whether
eristostatin made the melanoma cells better targets for natural killer
Brett Hensley ('07) did the first studies ever on intracellular signalling within melanoma cells following eristostatin exposure. Dara Missan ('06) studied how melanoma cells can vary in their metastatic potential as well as their tumor suppressor and tumor promoter gene expression.
Stephanie DiRosato ('08) studied how five groups of melanoma cells have their intracellular phosphorylation change when incubated with eristostatin.
Mollie Kostielney ('09) did cytotoxicity assays using NK cells and six types of melanoma cells. Alaa Mahmoud ('10) continued those experiments with a flow cytometric method. Liana Sherrod ('10) did the first ever adhesion experiments with atomic force microscopy.
Sarah Greenwood has developed an affinity-labeled anti-eristostatin column for isolating molecules crosslinked to eristostatin. Stefan Hailey's master's thesis deals with the changes in cell surface unbinding forces when melanoma cells are in contact with eristostatin and/or natural killer cells. Ryan Penn has compared the integrin repertoire of melanoma cells after an extended number of in vitro cell passages. He has also visualized the growth and apparance of melanoma cells in 3D gels. Brendan Mooney continued Stephanie DiRosato's project on intracellular signalling in melanoma cells exposed to eristostatin.
1Effect of the disintegrin eristostatin on hematogenous metastasis in three models of human malignant melanoma. Poster #5911, Proceedings of the American Association for Cancer Research 44: 1180, 2003.
2 McLane MA, Kuchar, MA, Brando C, Santoli D, Paquette-Straub CA, Miele ME. New insights on disintegrin-receptor interactions: Eristostatin and melanoma cells, Haemostasis 31: 3-6, 177-182, 2001.
Medical Technology department