Mark E. Welker

Mark E. Welker

Contact Info

Mark Welker

Chemistry Department Chair
William L. Poteat Professor of Chemistry

B.S. Chemistry with Highest Honors, University of North Carolina at Chapel Hill (1981);
Ph.D., Florida State University (L.S. Liebeskind) (1985);
Postdoctoral Fellow (Exxon & NIH), University of California-Berkeley (K.P.C. Vollhardt) (1985-86).
Elected a Fellow in the American Association for the Advancement of Science (AAAS) 2008. Dreyfus Foundation Henry Dreyfus Teacher-Scholar Awardee (1994-99).
Program Officer, Division of Chemistry, Organic and Macromolecular Chemistry Program, National Science Foundation, 2001-2002 and 2005 (off site).
Associate Provost for Research 2003-2008, Associate Provost for Research and Faculty Affairs 2008-2010, Vice Provost 2010-2011, Interim Provost 2011-2012.

Office: Salem 207C / 15A
Phone: (336) 758-5758
Email: welker@wfu.edu

Window on Wake Forest Research Article
Biographical Sketch

Research Group

Dr. Welker’s Research Group

Welker Lab Group photo

Research Description

Transition-Metal Mediated Organic Synthesis/Synthetic Methods/Medicinal Chemistry/Chemical Cancer Biology

1) Synthesis and Tandem/Sequential Reactions of Main Group element( Boron and Silicon) Substituted 1,3-Dienes.

The Welker group has pursued the research area of metal-mediated Diels-Alder (DA) reactions for several years. In the last five years (CHE-0450722 and 0749759), we began to prepare some new main group element substituted dienes and we have just begun to tackle their catalytic Diels-Alder chemistry. We have now prepared both boron and silicon-substituted dienes and started to study their tandem reactions.

2) Synthesis and Characterization of Novel Prostate Cancer-Targeted PI3 Kinase Inhibitor Prodrugs (collaborators George Kulik, Fred Salsbury).

The phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway is constitutively activated in a significant proportion of advanced prostate tumors, and is considered one of the key mechanisms supporting progression toward an androgen-independent status, for which no effective therapy is available. Recent data coming from clinical trials using the PI3K inhibitors, alone or in combination with other cytotoxic drugs, suggest that they might be a promising adjuvant tool to treat cancer with a constitutive activated PI3K/Akt pathway. In order to target advanced prostate cancer with the constitutively activated PI3K/Akt pathway, we are synthesizing PI3 kinase inhibitors which can be linked to a peptide which is a substrate for Prostate-Specific Antigen (PSA) protease. We are preparing analogs of know PI3 kinase inhibitors which can be linked to PSA cleavable peptides and hence will function as prodrugs for the treatment of prostate cancer.

3) High Performance Organic Thin Film Transistors (collaborator Oana Jurchescu)

Organic thin film transistors (OTFTs) could enable the development of next generation low cost, flexible electronics but they suffer from inadequate performance and high- power requirements. We are preparing novel halogenated self-assembled monolayer (SAM) dielectrics to simultaneously control film microstructure and induce a high charge density in the device channel. Synthetic organic chemistry reactions are used to prepare halogenated small molecules which are then self-assembled and tested on silica surfaces.

4) Modification of Naturally Occurring Polysaccharides for Use in Regenerative Medicine

Hyaluronic acid and alginate are naturally occurring polysaccharides which can be chemically modified to change their properties.  The Welker lab has been modifying these polysaccharides by converting their carboxylic acid functional groups into amides.  In the case of alginate, this modification is being performed to alter the acid-base stability of alginate pellets used for drug delivery.  Preliminary work shows that modified alginate is stable to acid environments similar to what one would find in the stomach and that these pellets disintegrate readily in a basic environment similar to what one would find in the small intestine.  The Welker lab is also modifying the chemical structure of naturally occurring hyaluronic acid (HA) with the goal of improving HA’s adhesive properties and its rigidity thereby improving its performance as a wound healing aid.  The Welker lab is also simultaneously synthesizing small molecules which could be used as modular additives to existing HA with hopefully similar improved performance outcomes for patients.

Publications

(75) Syntheses of 2-Silicon Substituted 1,3-Dienes.  Partha Choudhury, Christopher Junker, Ramakrishna Pidaparthi, and Mark E. Welker, Journal of Organometallic Chemistry,2014754, 88-93; http://dx.doi.org/10.1016/j.jorganchem.2013.12.046.

(74) Recent Syntheses of PI3K/Akt/mTOR Signaling Pathway InhibitorsMark E. Welker* and George Kulik*, Invited Review article submitted to Bioorganic and Medicinal Chemistry, 2013, 21, 4063-4091; http://dx.doi.org/10.1016/j.bmc.2013.04.083. 

(73) Metal Catalyzed Tandem Diels-Alder/Hydrolysis Reactions of 2-Boron-Substituted 1,3-Dienes.  Liqiong Wang and Mark E. Welker, Journal of Organometallic Chemistry, 2013, 723, 15-18; http://dx.doi.org/10.1016/j.jorganchem.2012.10.023.

(72) Preparation and Diels-Alder/Cross Coupling Reactions of New 2-Boron-Substituted 1,3 –Dienes.  Liqiong Wang and Mark E. Welker, Journal of Organic Chemistry, 2012, 77, 8280-8286; http://dx.doi.org/10.1021/jo3016727.                                                                                          

(71) Synthesis and Characterization of a Novel Cancer-Targeted PI3 Kinase Inhibitor Prodrug.  Daniele Biaz, Tanya A. Pinder, Sazzad Hassan, Yelena Karpova, Freddie Salsbury, Mark E. Welker, and George Kulik.  Journal of Medicinal Chemistry, 2012, 55, 8038-8046; http://dx.doi.org/10.1021/jm300881a.  Selected as the cover paper for the November 26, 2012 issue of J. Med. Chem.; http://pubs.acs.org/action/showLargeCover?jcode=jmcmar&vol=55&issue=22

(70) Ruthenium Carbenes as Multi-Task Catalysts in Stereoselective Ene-Yne Metathesis/Diels-Alder and Ene-Yne Metathesis/Diels-Alder/Cross Coupling Multicomponent Reactions.  Christopher S. Junker and Mark E. Welker, Tetrahedron, 2012, 68, 5341-5345, http://dx.doi.org/10.1016/j.tet.2012.05.011.

Awards & Accomplishments

William L. Poteat Professor of Chemistry, 2005-present
Elected AAAS Fellow, 2008