MasterGlam is thrilled to launch our new "Amazing Women" series to profile women leading the charge in the fields of STEM and commerce. This week, we are highlighting the story of Dr. Mandë Holford, an American scientist leading the charge in our nation's biotechnology arms race.
Venomous creatures make up 15% of our biodiversity. Dr. Mandë Holford’s lab has been using a variety of techniques to study and characterize venom peptides that work at a molecular level to disrupt the way that our cells function. These are the same peptides that work with the precision of a Swiss Army Knife to help our bodies naturally produce structural proteins like collagen and Keratin
They also can cause the neurons in our cells to function abnormally and even cause our cell's membrane walls to rupture. Her lab is working to identify novel peptide-based therapies that can be used like an on/off switch to switch off the body's nature to supply tumors with viable cells to address the medical needs of patients undergoing treatment for AIDS and various types of cancer. Dr. Holford’s groundbreaking research has already shown that venom peptides can induce apoptosis (programmed cell death), prevent metastasis (cancer spreading to a different site), and inhibit angiogenesis (the formation of new blood vessels that feed tumors).
Her research team at the Holford Lab has been using a variety of techniques to study venom peptides, including phylogenetic (evolutionary) mapping and high-throughput transcriptomic (study of RNA molecules and their expression patterns) and proteomic (study of protein molecules and their expression patterns) analyses to identify peptide sequences that make up the venom arsenal. After mapping out the relationships between species, her team extracts RNA from the tissue in the venom gland and sequences them using next-generation sequencing (NGS) techniques. Her team further analyzes all of the compounds that the snail is making when harvested by milking protein from the venom gland and analyzing it using liquid chromatography-mass spectrometry (LC-MS). Dr. Holford also conducts in vivo whole animal screening using fruit flies to understand which compounds are the most effective.
However, one of Dr. Holford's most significant breakthroughs was the discovery of Ziconotide and the subsequent commercialization of Prialt. About 1000 times stronger than the most potent painkilling agent, ziconotide was derived from the venom of the cone snail (Conus magus) and is used to treat pain caused by cancer and HIV. Dr. Holford's work on Ziconotide was groundbreaking because it was discovered through the evolutionary branching of venomics, rather than the traditional form of data collection based on size and weight. Dr. Holford’s work highlights the importance of exploring the vast biodiversity of our planet to unearth new sources of medicines and other valuable compounds. Dr. Holford also demonstrates that with the power of modern sequencing, it is possible to conduct such research without harming the ecosystems and achieve better long-term results compared to chemotherapy.
|
Venom Type |
Approved by FDA |
Medical Use |
|
Gila Monster |
2005 |
Lowers blood sugar for type 2 diabetes patients |
|
Brazilian Pit Viper |
1981 |
Reduces blood pressure for hypertension patients |
|
Cone Snail |
2004 |
Delivered around base of the vertebral column. Goal: to help control long-term pain from cancer and other long-term illnesses |
Dr. Holford is now carving out a new footprint in the edtech sector. She created the online games company "Killer Snails" to advance accessibility and promote STEM learning in the K-12 segment. The games focus on educating students about biodiversity and how venomous animals have evolved unique mechanisms for survival.
The Holford Lab has collected 199 species and mapped over 1700 specimens over the course of her distinguished career. Dr. Holford is now partnering with Dr. Jackie Faherty on a new initiative, 2030STEM, which aims to increase early- and mid-career representation of Black, Latino/a/X, Indigenous, and other underrepresented minorities in STEM.
References
Gloucester Marine Genomics Institute. (2021). Gmgi Science Hour — Venom Attacks Cancer w/ Dr. Mandë Holford. GMGI Science Hour. Retrieved April 13, 2023, from https://www.youtube.com/watch?v=n426AkaJkGc&t=2488s.
Dr. Mandë Holford, Associate Professor, Hunter College, The American Museum of Natural History, CUNY Graduate Center discusses her experience transforming sea snail venom into modern medicine with Chris Bolzan, Executive Director of Gloucester Marine Genomics Institute.