Anti-microbial Drugs

Over the years, bacteria, fungi and protozoa have increasingly developed resistance to traditional antibiotics. In particular fungi and protozoa are recognized as emerging problems; in the past 25 years the number of life threatening infections caused by these organisms due to their resistance to traditional drugs has been growing. Research on new medicines to fight these infections is a focus of our labs. In collaboration with Chris Dykstra and Scott Franzblau we are targeting enzymes in these organisms that synthesize necessary components of their cell walls. The cell wall is an attractive target since it is required by the pathogens for growth, but has no counterpart in humans and other mammals.

Cancer Therapy

The simplest description of cancer is uncontrolled cell growth. In collaboration with Lee Wattenberg, Kris Pankiewicz and Dan Billadeau our lab is interested in stopping growth of tumors by causing tumor cells to differentiate or by interfering with cell signaling pathways involved with cell growth. This based on the concept that cancer cells are normal cells that are trapped in an immature (or less differentiated) state, where they lack the ability to control their own growth. We have designed and synthesized a class of molecules that causes differentiation of many types of cancer cells. This does not destroy the cancer cells, but instead causes them to mature into cells that can regulate their own growth. This approach is less toxic than conventional chemotherapy, which attempts to kill the cells completely.

Antiviral Therapy

In collaboration with Lou Mansky we are investigating the effect of novel combination therapy and its potential for clinical use as treatment for viral infections such as HIV and Hepatitis.

Cyanide Antidotes

Cyanide is a well known toxin with potential as an international threat, a weapon of mass destruction and an accidental hazard through industrial exposure, medical crisis or smoke inhalation. Current treatments for cyanide poisoning are slow acting and can have serious life threatening side effects. In collaboration with Herb Nagasawa and Bob Vince we are developing a series of andidotes that use a ubiquitous enzyme that converts cyanide to a non-toxic substance. We have shown that our antidotes are more effective than the current treatments. In addition, our treatments work prophylactically. Currently we are working to expand our series of antidotes, to improve their efficacy in reversing cyanide toxicity, and to move these potential treatments into clinical trials.

Synthetic Methods

Because many drug design projects involve molecules known as nucleosides, nucleotides, and carbohydrates, our group is interested in finding improved ways to make these molecules.

Recent Publications (For detailed publication list: Click Here)

Back to the future: revisiting HIV-1 lethal mutagenesis. Dapp MJ, Patterson SE, Mansky LM. Trends Microbiol. 2012 Nov27;Ahead of Print; DOI:10.1016/j.tim.2012.10.006. Abstract

IP-FCM measures physiologic protein-protein interactions modulated by signal transduction and small-molecule drug inhibition. Smith SEP, Bida AT, Davis TR, Sicotte H, Patterson, SE, Gil D, Schrum AG. PLoS One. 2012 Sep 21;7(9):e45722. Abstract

Anti-HIV-1 activity of resveratrol derivatives and synergistic inhibition of HIV-1 by the combination of resveratrol and decitabine. Clouser CL, Chauhan J, Bess MA, Oploo, JL, Zhou D, Dimick-Gray S, Mansky, LM, Patterson SE. Bioorg. Med. Chem. Lett. 2012 Nov 1;22(21):6642-6. Abstract

Cyanide Toxicity in Juvenile Pigs and Its Reversal by a New Prodrug, Sulfanegen Sodium. Belani KG, Singh H, Beebe DS, George P, Patterson SE, Nagasawa HT, Vince R. Anesth. Analg. 2012 Mar;114(5):956-61. Abstract

Activity of a Novel Combined Antiretroviral Therapy of Gemcitabine and Decitabine in a Mouse Model for HIV-1. Clouser CL, Holtz CM, Mullett M, Crankshaw DL, Briggs JE, O'Sullivan MG, Patterson SE, Mansky LM. Antimicrob Agents Chemother. 2012 Apr;56(4):1942-8. Abstract

Discovery of drugs that possess activity against feline leukemia virus. Greggs WM 3rd, Clouser CL, Patterson SE, Mansky LM. J Gen Virol. 2012 Apr;93(Pt 4):900-5. Abstract

The combination of cobinamide and sulfanegen is highly effective in mouse models of cyanide poisoning. Chan A, Crankshaw DL, Monteil A, Patterson SE, Nagasawa HT, Briggs JE, Kozocas JA, Mahon SB, Brenner M, Pilz RB, Bigby TD, Boss GR. Clin Toxicol (Phila). 2011 Jun;49(5):366-73. Abstract

Broadening the use of antiretroviral therapy: the case for feline leukemia virus. Greggs WM 3rd, Clouser CL, Patterson SE, Mansky LM. Ther Clin Risk Manag. 2011; 7:115-22. Abstract

Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine. Clouser CL, Holtz CM, Mullett M, Crankshaw DL, Briggs JE, Chauhan J, VanHoutan IM, Patterson SE, Mansky LM. PLoS One. 2011 Abstract

Phosphonoxins III: synthesis of α-aminophosphonate analogs of antifungal polyoxins with anti-giardia activity. Staake M, Chauhan J, Zhou D, Shanker A, De Chatterjee A, Das S, Patterson SE. Org Lett. 2010 Oct 15;12(20):4596-9. Abstract