Laura M Sanchez
Medicinal Chemistry and Pharmacognosy with a courtesy appointment in Chemistry
833 S. Wood St. 321 PHARM, MC 781
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The Specialized Metabolites of Pathogenesis
Biofilms are sessile surface-attached bacterial communities encased in a complex matrix. Biofilm formation is a contributing factor to virulence and persistence of up to 80% of microbial infections in the human body. It is, therefore, of the utmost importance to detect these pathogens in the biofilm state prior to infection of a host. The Sanchez lab will use state-of-the-art MS techniques to study the specialized metabolites involved in biofilm formation in two clinically relevant Gram-negative pathogens. Defining the specialized metabolites of pathogenesis will allow us to test the hypothesis that there are specific specialized metabolites produced by the pathogens in the biofilm state that can be monitored using mass spectrometry techniques to detect biofilm-forming potential prior to infection of a host.
In nature, organisms exist in close physical proximity and often either compete for resources or rely on metabolic exchange for community survival. Cheese rind communities are relatively simple mixed microbial communities (~10-12 microbes/rind) and these communities can be recapitulated in a lab setting. Proper microbial community composition is essential in cheese aging for flavor as well as ensuring that the surface of the cheese is not contaminated by food pathogens. There has been increasing speculation that the microbes we ingest may play a role in our overall health so understanding microbial growth events and the specialized metabolites these microbes make allows us to deepen our understanding of how different factors can contribute to overall human health. In collaboration with Rachel Dutton’s laboratory at UC San Diego and Benjamin Wolfe's lab at Tufts University, we are investigating how microbial pairs isolated from cheese interact with one another.
In high grade serous ovarian cancer, the 5-year survival rate is less than ten percent, and there are an estimated 21,000 new cases each year of ovarian cancer, with 14,000 women succumbing to the disease each year. A contributing factor to these numbers occurs because most patients present with widespread disease at the time of diagnosis due to a lack of diagnostic tests. Goal 2 of the Office of Research on Women’s Health (ORWH) Strategic Plan calls for ‘work toward devising minimally invasive technologies for rapid and accurate screening, diagnosis, and treatment of diseases.’ In collaboration with Joanna Burdette's lab at UIC, we seek to (1) exploit and expand our knowledge of imaging mass spectrometry (IMS) to probe the small molecule signaling that governs early metastasis of ovarian cancer and (2) identify molecular signatures for various types and stages of ovarian cancer. Funding: NIH K12 BIRCWH scholarship (2016-2018, Completed), UIC CCTS Pilot Grant.
Host- Microbe Chemical Communication
A major area of research is now dedicated to how beneficial bacteria—our “microbiome”—are required for nutrient acquisition, immune and tissue development, and to preferentially occupy niches that otherwise can be overtaken by pathogens. Bacteria dedicate up to 25 % of their genetic material to chemistry, but little is known about how bacteria use chemistry in a host. Therefore a major question now is to understand how chemical communication between the host and colonizing microbe mediate specific interactions. This project integrates the technological expertise of the Sanchez Lab and the animal and genetic expertise of the Mark Mandel Lab.
1. Galey MM, Sanchez LM. "Spatial analyses of specialized metabolites: the key to studying function in hosts." mSystems, 2018; 3(2): e00148-17.
2. Ochoa JL, Sanchez LM, Koo B-M, Doherty JS, Rajendram M, Huang KC, Gross CA, Linington RG. “Marine mammal microbiota yields novel antibiotic with potent activity against Clostridium difficile.” ACS Infectious Disease, 2018; 4(1): 59-67.
3. Cleary JL, Condren AR, Zink KE, Sanchez LM. Calling all hosts: bacterial communication in situ. Chem, 2017; 2(3): 334-358.
4. Garg N, Zeng Y, Edlund A, Melnik AV, Sanchez LM, Mohimani H, Miao V, Schiffler S, Lim YW, Luzzatto-Knaan T, Cai S, Rohwer F, Pezner PA, Cichewicz RH, Alexandrov T, Dorrestein PC. The spatial molecular architecture of the microbial community of Peltigera Lichen. mSystems, 2016;1(6): e00139-16.
5. Nguyen DD, Melnik AV, Koyama N, Lu X, Schorn M, Fang J, Aguinaldo K, Lincecum Jr TL, Ghequire MGK, Carrion VJ, Cheng TL, Duggan BM, Malone JG, Mauchline TH, Sanchez LM, Kilpatrick AM, Raaijmakers JM, Mot RD, Moore BS, Medema MH, Dorrestein PC. Indexing the Pseudomonas specialized metabolome enabled the discovery of poaeamide B and the bananamides. Nature Microbiology, 2016; 2, 16197.
B. A., Chemistry
Univeristy of California, Santa Cruz