Graduate NIH Training in Biotechnology
Former Trainees
Joel Kaar
PhD Chemical Engineering, University of Pittsburgh, December 2007.
Currently a
post-doc at the University of Cambridge, Laboratory of Molecular Biology.
Project Description
Under the direction of Dr. Alan Russell, my research has focused primarily on exploiting fundamental relationships between enzyme structure, function, and molecular environment to improve biocatalyst efficiency. Much of my research has been conducted within the fields of non-aqueous biocatalysis, bioremediation, and tissue engineering with an emphasis on the convergence of enzymes and materials.
One area of research that I have been actively involved has included exploring the use of ionic liquids (organic salts that have unusually low melting points and lack any vapor pressure) as green solvents for enzymatic reactions. Using lipase as a model enzyme, we have probed the impact of ionic liquid physical properties on enzyme activity and stability.
I have also worked extensively on the development of a novel approach to pH control in the biocatalytic detoxification of organophosphate (OP) nerve agent stockpiles. Acid produced by the enzymatic hydrolysis of OP agents may inactive the enzyme prior to complete detoxification if the reaction is not effectively buffered. The underlying challenge in buffering the pH in such reactions is the need for tremendous amounts of conventional buffers, which may be required at concentrations that exceed their solubility limit and may inhibit the agent-degrading enzyme. An alternative approach to pH control in OP hydrolysis reactions is to balance the production of acid with the enzymatic generation of base. In this way, a dynamic pH equilibrium is created between the opposing reactions, essentially mimicking how cells manipulate their internal pH. We have successfully demonstrated biocatalytic pH control by coupling the simultaneous biocatalytic hydrolysis of the model OP agents paraoxon and diisopropylfluorophosphate with that of urea.
Another area of my research has involved the development of an enzyme-based therapy for reversing the effects of scarring in skeletal muscle. A barrier in the body’s natural healing process is the formation of dense fibrotic (i.e. scar) tissue, which blocks progenitor cells from infiltrating the injured sire where they can differentiate into new tissue. The end result of scarring in muscle injuries is the inhibition of full functional recovery and the increased likelihood of re-injury. Existing therapies are based solely on scar prevention and hence such treatments offer little to no benefit if not administered with a shor time period post-injury. We are investigating the therapeutic effectiveness of delivering exogenous matrix metalloproteinase-1 (MMP-1), a protease that targets extracellular matrix proteins of which scar tissue is comprised, may degrade pre-exisiting scar and is likely to prevent scar formation altogether if administer during healing. Having shown MMP-1 to be effective in reversing scarring in an animal model, we are now exploring means of improving the in vivo stability, and thus benefit, of MMP-1 by chemical modficiations to the surface of the enzyme.
Course work
Fundamentals of Thermodynamics
Fundamentals of Reaction Processes
Mathematical Methods in Chemical Engineering
Fundamentals of Transport Processes
Fundamentals of Biochemical Engineering
Introduction to Cell and Molecular Biology
Foundations of Biomedical Sciences
Foundations of Biomedical Sciences Conference
Principles of Pharmacology
Stem Cells
Scientific Ethics
Issues in Research and Teaching
Publications
Kaar JL, Li Y, Blair HC, Russell AJ. Improving the therapeutic effectiveness of MMP-1 in reversing the effects of scarring in skeletal muscle. (In preparation)
Kaar JL, Depp V, Russell AJ, Lele BS. Preparation of highly solvent soluble biocatalysts by tryptophan specific interactions with amphiphilic comb polymers. (In preparation)
Kaar JL, Oh H, Russell AJ, Federspiel WJ. Towards improved artificial lungs through biocatalysis. Biomaterials (In press)
Bedair H, Liu TT, Kaar JL, Shown B, Russell AJ, Huard J, Li Y. Matrix metalloproteinase (MMP) therapy improves muscle healing. J Appl Physiol (In press)
Xu H, Kaar JL, Russell AJ, Wagner WR. Characterizing the modification of surface proteins with poly(ethylene glycol) to interrupt platelet adhesion. Biomaterials 2006;27(16):3125-3135.
Sharma NK, Tickell MD, Anderson JL, Kaar J, Pino V, Wicker BF, Armstrong DW, Davis JH Jr, Russell AJ. Do ion tethered functional groups affect solvent properties? The case of sulfoxides and sulfones. Chem Commun 2006;6:646-648.
Russell AJ, Kaar JL, Berberich JA. Using biotechnology to detect and counteract chemical weapons. The Bridge (a publication of the Nation Academy of Engineering) 2003;33(4):19-24.
Berberich JA, Kaar JL, Russell AJ. Use of salt hydrate pairs to control water activity for enzyme catalysis in ionic liquids. Biotechnol Prog 2003;19(3):1029-1032.
Kaar JL, Jesionowski AM, Berberich JA, Moulton R, Russell AJ. Impact of ionic liquid physical properties on lipase activity and stability. J Am Chem Soc 2003;125(14):4125-4131.
Russell AJ, Erbeldinger M, DeFrank JJ, Kaar J, Drevon G. Catalytic buffers enable positive-response inhibition-based sensing of nerve agents. Biotechnol Bioeng 2002;77(3):352-357.
Patents
Oh H, Kaar JL, Russell AJ, Federspiel WJ. US provisional entitled "Devices, systems and methods for reducing the concentration of carbon dioxide in fluids.”
Seminars
Chemical Engineering Department Graduate Student Seminar Series, University of Pittsburgh
Bioengineering Department Graduate Student Seminar Series, University of Pittsburgh
Musculoskeletal Research Center Seminar Series, University of Pittsburgh
McGowan Institute Distinguished Lecture Series, University of Pittsburgh
Advisor
Alan J. Russell
University Distinguished Professor of Surgery, Bioengineering and Chemical Engineering
Director, McGowan Institute for Regenerative Medicine
University of Pittsburgh
