Matthew Black
- Graduate researcher

Office : MRL 2042, (805) 893 7923
Lab : MRL 1050, (805) 893 7941
mblack@engineering.ucsb.edu

Resume

The overall goal of my work is to use peptide amphiphiles to create self-assembling synthetic aggregates, such as micelles or vesicles, to create therapies for tumors and cardiovascular disease. I am also addressing fundamental issues, such as understanding mixed micelle formation from peptide amphiphiles. Currently, I am studying peptide amphiphile systems that can target tumors, penetrate cells, and cause apoptosis in cancer cells.

There are many problems currently associated with cancer treatments, such as the toxicity of cancer drugs to normal cells and cancers becoming resistant to specific drug treatments. For these reasons, it is desirable to have a single particle that would be able to deliver multiple treatments locally to a tumor. We believe that creating mixed micelles from peptide amphiphiles will allow us to efficiently incorporate multiple functions into a single particle and be a valuable tool in treating cancer.

Systemic side effects from chemotherapy are a major obstacle in current cancer treatments. However, tumors and individual cancer cellshave specific markers that are related to and often required for the growth of the tumor. Often times, these markers are distinct from the normal cells and organs surrounding the tumor. We have identified peptides that specifically target tumors in collaboration with Patrick Daugherty’s lab and Erkki Ruoslahti’s lab. We are incorporating these peptides into micelles in order to bring a payload (imaging agent, drug, pro-apoptotic peptide, etc.) exclusively to tumors, which will help avoid the systemic side effects from most current cancer treatments and require lower doses to be administered.

In addition to the targeting peptides, I am also studying a pro-apoptotic peptide from the BH3 domain of the Bid protein. The peptide has been shown to free Bak/Bax from anti-apoptotic Bcl-2-like proteins and activate Bak/Bax to form pores in the mitochondrial membrane , which causes cells to undergo apoptosis. The Bid-BH3 domain peptide requires an alpha helical structure for binding. Our lab has previously shown that incorporating peptides into micelles can increase their secondary structure significantly . We theorize that incorporating the Bid BH3 domain peptide amphiphile into mixed micelles will increase the secondary structure of the peptide and increase its binding affinity. Combining a drug and a BH3 domain peptide into the same treatment has previously shown to greatly increase the efficacy compared to either treatment used alone .  Incorporating the peptide into mixed micelles will also allow us to easily add other functions, such as a hydrophobic drug.

It is possible that a micelle with drug and/or pro-apoptotic peptide will not easily get into cells, even if targeted to tumors with specific peptides. In this case, we plan to incorporate a peptide, such as pTAT or poly arginine, that has previously been shown to effectively bring payloads into cells.

I will create and optimize a multifunctional micelle that will to incorporate all of these functions to treat cancer.  I will show that peptide amphiphiles that self assemble into mixed micelles are an efficient way to bring multiple functionalities into a single particle.