New Grant Funding

I'm pleased to announce that I have been awarded an internal Academic Health Center Seed Grant for a new project titled "Mechanism of Action of RITA, a Small Molecule for MLL Leukemias" for 2011–2012. Although the grant is small, $25,000, it will be a big help in getting this new project off the ground. This is a project that I have recently begun with Professor John Kersey, the Founding Director of the Masonic Cancer Center, as well as my medicinal chemistry colleague, Dan Harki. The structure of RITA (NSC 652287, below) is rather simple, but its anticancer activity is extremely intriguing and has provided us with many avenues to study.

Congratulations to Will Fiers

This past Thursday, July 28, Will Fiers successfully passed his Preliminary Oral Examination! Will is a second-year graduate student in the lab, and he did an exceptional job in defending his written proposal, "Synthesis and Biological Activity of Constrained 7-Oxozeaenol Derivatives." He is now officially a Ph.D. candidate. Congratulations are in order to Will for passing this milestone!

Seminars This Week

Today is the day that I'm proud to be hosting Scott Snyder from Columbia University for his seminar at noon titled "Lessons in Chemoselectivity: Total Synthesis of Polyphenolic Natural Products" in 7-135 Weaver-Densford Hall. Scott and I overlapped at Scripps for a couple years, so it will be great to hear about the success of his independent research program at Columbia.

Alison Frontier from the University of Rochester will then be on campus this Wednesday and Thursday for the latest Abbott Workshop Series in Synthetic Organic and Medicinal Chemistry hosted by the Department of Chemistry. Her seminar, "New Twists in Nazarov Cyclization Chemistry," will be on Wednesday at 4:15 pm in 331 Smith Hall. The workshop discussion will be held on Thursday, July 14 at 10:00 am in 114 Science Teaching & Student Services. This will be followed by a pizza lunch, and the Fecik group meets with Alison from 1:30-2:15 pm.

Seminars Next Week

There are three seminars of interest taking place next week. On Monday, June 27, Dr. Henry Wong will present his talk "Adnectins: A Novel Class of Targeted Protein Therapeutic" in 7-135 Weaver-Densford Hall at 11:00. Dr. Wong is a candidate for the Pharmacologist position in ITDD.

As part of the Medicinal Chemistry Seminar Series, Kathryn Nelson, a third-year graduate student in Courtney Aldrich's lab, will present her research seminar titled "Total Synthesis and Biological Evaluation of the Siderophore Acinetobactin and the Structurally Related Natural Product (+)-Transvalencin Z" on Tuesday, June 28 in 7-135 Weaver-Densford Hall at 11:30. Lunch will be provided, but you will need to bring your own drink.


Lastly, the Microbiology, Immunology, and Cancer Biology (MICaB) program will be hosting Dr. Bill Phelps as part of their Career Development Seminar Series. Bill is a Program Director at the American Cancer Society (ACS), and he leads the ACS study section on Cancer Drug Discovery on which I have served. He will be speaking at 12:00 noon on Thursday, June 30 in 450 MCRB, and the title of his talk is "Perspectives on Cancer Research from a Career Path in Academia, Government, Industry and a Private Foundation" and "How The ACS Supports Cancer Research." Bill is a Minnesota alumnus and he received his Ph.D. in Microbiology in 1985 at Minnesota. Prior to his appointment at ACS in 2001, he was a postdoc at NCI and a scientist at Burroughs-Wellcome/GlaxoWellcome/GlaxoSmithKline for several years. Bill's a great person, and he will provide a fascinating insight to cancer research and grant funding. Lunch will be provided, but you must RSVP for lunch here by Wednesday, June 29 at noon.

Fall Chemical Biology Interest Group Meetings Announced, Group Meeting Updates

The Fall 2011 meeting schedule for the monthly Chemical Biology Interest Group has been announced. The calendar has been updated with the following dates:


Thursday, August 18: Finzel and Xing groups
Thursday, September 15: Wagner and Aldrich groups
Thursday, October 20: Distefano and Amin groups
Thursday, November 17: Harki and Fecik groups


All meetings begin at 6:30 pm in 7-135 Weaver-Densford Hall, and pizza will be served.


Details for the summer Fecik-Georg joint group meetings have been updated through August (see calendar). Due to various out of town commitments, including the Fall National American Chemical Society Meeting, group meetings for August have been canceled. Meetings will resume again in September.

Chemistry Biology Interface Training Grant Symposium Recap

Chemistry-Biology Interface Training Grant Symposium

Wednesday, May 25, 2011

University of Minnesota, Mayo Auditorium

The Chemistry Biology Interface Training Grant Symposium is held annually as part of the University of Minnesota's NIH-funded grant of the same name. The day's events included a midday poster session and mix of external and internal speakers, including a grant trainee.


Mark Distefano opened the morning with introductory remarks before the first speaker, Rami Hannoush from Genentech. His talk, "Chemical Probes for Inhibiting Wnt Signaling and Visualizing Protein Fatty Acylation," was focused on two subjects. The first part was centered around his work on studying protein-protein interactions and assembly of Wnt signaling complexes in order to discover drugs that interrupt Wnt signaling for cancer. Switching gears, Rami then presented research on the use of fatty acid analogs for imaging protein modification by lipids. This was a fantastic talk that demonstrated the power of new methods for the design of biological probes useful in drug discovery.

Rami Hannoush (Genentech) with Professor Yusuf Abul-Hajj.

Click picture to see more photos from the symposium.

Next up was Leah Randles, a fifth year graduate student and 2007–2009 grant trainee from Kylie Walters' lab, with her talk "Regulation of the Proteasomal Ubiquitin Receptor Rpn13." She presented a lot of intriguing work on using various NMR solution structures to study the role of hPLIC2 as a negative regulator of Rpn13 activity. Leah fielded a lot of questions and spoke with many people about her findings after the talk.


Over 30 posters were presented over lunch in the lobby of Mayo Auditorium. There were a lot of outstanding posters, and much discussion ensued amongst the participants during the 90 minute session.

Intense studying at the poster session.

Click picture to see more photos from the symposium.

Following lunch and the poster session was Professor Adrian Hegeman from the Department of Horticultural Sciences at Minnesota with a presentation entitled "Plant Metabolomics Methodology: Using in Vivo Stable-Isotope Labeling for Elemental Composition Assignments." I was unfamiliar with his work, so this talk was a fascinating insight as to how plant metabolomics can be used to study plant behavior and production of nutrients and responses to stress.


Joseph Beckman from Oregon State University then provided a thought-provoking talk on peroxynitrite, superoxide dismutase (SOD), and amyotrophic lateral sclerosis (ALS) titled "Oxidative Stress and the Chemical Biology of Neurodegeneration: Did Free Radicals Kill Lou Gehrig?" Much of the talk focused on post-translational modification of proteins by nitration of tyrosine residues and evidence that mutations to SOD are involved in ALS. The role of nitration in the regulation of protein function, particularly Hsp90, was also presented.


I unfortunately had to miss the final lecture of day delivered by Leona Samson from MIT on "Complex Biological Responses to DNA Damage." The entire event was a wonderful learning experience, and the organizing committee did an exceptional job of delivering a fantastic program that reflects the diversity and importance of chemical biology research.

Seminars Next Week

It's great that seminars continue here throughout the summer, and three have been announced for next week. On Monday, June 20 Lih-Wen Deng from the National University of Singapore we present "Function of Mixed Lineage Leukaemia 5 in Cell Cycle Regulation" as part of the Chemical Biology Colloquium series. The talk will in 3-100 Mayo Auditorium at 12:15 pm, and pizza and beverages will be served.

The summer Medicinal Chemistry seminar series will kick off on Tuesday, June 21 with a graduate student presentation from Amit Gangar (Wagner lab) at 11:30 am in 7-135 Weaver–Densford Hall. Amit's talk is titled "Design and Development of Bispecific Chemically Self-Assembled Nanostructures for Anti-Cancer Drug Delivery." Lunch will be provided, but BYOB (bring your own beverage).


A special seminar will be given on Wednesday, June 22 at 9 am in 7-135 Weaver–Densford Hall by Dr. Krishnan Subbiah titled "Targeted Oncology Therapeutics: In Vivo Pharmacology." Dr. Subbiah is a candidate for the Pharmacologist position in the Institute for Therapeutics Discovery and Development.

It will be busy seminar week, but I'll see everyone there!

Jesse Ventura's Prozac Ignorance

My daily break from all things serious is listening to "Darkness on the Edge of Town", the self-proclaimed "best in paranormal talk radio" show on 100.3 FM KTLK. Their guest last Monday was none other than former Minnesota Governor Jesse "The Body" Ventura, who is out promoting his latest book on conspiracy theories. Among the wacky ideas he was peddling was this doozy about fluoride in drinking water:


"Do you want to know who the first person was to put fluoride in water? The Nazis. Now I'll tell you why. Do you know what fluoride is the 90% main ingredient to? Prozac. So when you're drinking fluoride water you're essentially drinking liquid Prozac. That's called the dumbing down of society. Think about that. Yet they force it upon us and they tell us it's for our teeth."


You can download the June 6, 2011 episode from the KTLK website, and this comment was made at the 31:47 mark.


It's really disturbing that anyone would believe this, and even more disturbing that this type of sheer ignorance is being promoted by our former Governor. First, I'm not aware of any credible data that fluoride in drinking water has any type of mood-elevating or anti-depressant activity akin to Prozac. Second, there is no evidence that fluoride is released from Prozac when it is metabolized in humans. Lastly, fluorine is not the "90% main ingredient" of Prozac. Below is the chemical structure of Prozac (aka fluoxetine) and its elemental analysis showing that fluorine comprises approximately 18% of its molecular weight.

I'll let you draw your own conclusions about Governor Ventura's belief that this is a Nazi-inspired plot to control the entire United States population. 

Amber Onorato Invited to Natural Products Gordon Conference as Discussion Leader

Congratulations to Amber Onorato, a postdoc, on being invited to serve as Discussion Leader at the Gordon Research Conference on Natural Products this year! She was recently invited by the Program Chair, Karl Hansen (Amgen), to be Discussion Leader for one of the sessions on Pharmaceutical Process Chemistry. This year, the Gordon Conference will be held at Bryant University in Smithfield, RI from July 24–29. The Natural Products Gordon Conference is one of the premier international meetings in the field, and it's always an amazing experience to attend. It's perhaps my most favorite meeting, but unfortunately I cannot attend this year due to the expected arrival of a daughter the summer. Amber presented a poster at last year's meeting, and it's great that she has the opportunity to attend again as a Discussion Leader.

David Sherman - Abbott Workshop Recap

Professor David Sherman, University of Michigan

Abbott Workshop in Synthetic Organic Medicinal Chemistry

Friday, May 20 and Saturday, May 21, 2011

I had the distinct privilege of hosting my friend and collaborator, Professor David Sherman, from the University of Michigan on May 20 and 21 for the Abbott Workshop in Synthetic Organic Medicinal Chemistry in the Department of Chemistry. This was David's first seminar presentation at Minnesota since he left here for Michigan in 2003. The Abbott Workshop is a fantastic seminar series since it provides graduate students with extensive opportunities for interacting with prominent speakers in small groups and in a discussion-based workshop session.

David address the audience during his Friday afternoon seminar.

David with former postdocs Christine Salomon and Courtney Aldrich.

Following the usual day of visiting with chemistry faculty, lunch with students, and participation in the weekly Synthesis Literature Meeting, David presented his Friday afternoon seminar, "Novel Drug Leads from Natural Products and Their Derivation from Microbial and Biosynthetic Diversity." He began with an overview of the changes that have taken place in studying bacterial genetics and secondary metabolism and a description of his discovery efforts in Costa Rica as a teaser for the Saturday workshop. David then led the audience through some of his work on polyketide biosynthesis in three parts. First was a project-spanning walk through his ground-breaking work on pikromycin biosynthesis, subtitled "Interrogating Molecular Specificity in Modular PKSs." Having collaborated with David on much of this research, it was fascinating to realize how much has been accomplished in the study of macrolide antibiotics, yet also exciting at the opportunities that remain. The second part, "Biosynthetic P450s as a Tool for C–H Bond Activation," described his work in using PikC, a P450 tailoring enzyme in pikromycin biosynthesis, for the oxidation of a remarkable variety of non-natural substrates. Finally, new research that has been accepted for publication in Nature Chemistry on the unusual biosynthesis of tirandamycins was presented to close the talk.

Friday dinner at Sen Yai Sen Lek. L–r: Christine Salomon, Andy Harned, Tom Hoye, Chris Douglas, David Sherman.

Christine Salomon and Courtney Aldrich, both former postdocs of David's, and I chatted with David for a while after his talk, and I briefly showed him around our new labs in the 717 Delaware Building before heading to dinner at Sen Yai Sen Lek. David, Christine, Tom Hoye, Andy Harned, Chris Douglas, and I shared some delightful Thai food and a lot of laughs over David's stories from collecting expeditions in Costa Rica.

David presents his Saturday morning workshop discussion.

I met David for breakfast at Starbuck's on Saturday morning, and this offered us our first opportunity to catch up with each other and discuss some future project ideas. Beginning at 10 am, David led the packed room in a two and a half hour discussion about natural products discovery and his International Cooperative Biodiversity Group, which encompasses synergistic collaborations with Giselle Tamayo (INBio, Costa Rica), Jon Clardy (Harvard Medical School), Phil Crews (UC-Santa Cruz), Verenium (San Diego), the Joint Genome Institute (Berkeley), and Eisai. As you can imagine, the scope and objectives of the group are huge and ambitious. His informal presentation led into discussions about beetles and bioenergy production, marine sample collecting, political issues, and the study of symbiont biosynthetic pathways, including that of ET-743 (aka ecteinascidin 743, trabectedin, Yondelis). The pizza lunch arrived too quickly, and everyone seemed to enjoy the unique discussion. David's afternoon was spent meeting individually with the Fecik, Hoye, Harned, and Douglas research groups, and his visit ended with dinner Saturday evening with a group of students.


Overall, the two days with David were invigorating and stimulating, and his unique perspectives on modern natural products research were beneficial to all.


The next Abbott Workshop will be July 13 and 14, when the Department of Chemistry will be hosting Professor Alison Frontier (University of Rochester).