Directory ProfileCampus Directory
Mark S Kuhlenschmidt
Address and Contact Information
- PhD, Biochemistry, University of Pittsburgh, School of Medicine, Department of Biochemistry
- Postdoctoral Fellow, Johns Hopkins University
- MS, Biochemistry, University of Louisville, School of Medicine, Department of Biochemistry
- BS, Biology (major) Chemistry (minor), Purdue University
The long-term goals of my laboratory are to identify and exploit mechanisms of cell-cell recognition and adhesion for the development of new approaches for the prophylaxis and treatment of infectious disease as well as cancer cell metastasis. Our studies on infectious disease are focused on understanding the initial recognition, adhesion, and entry events that occur between the microbial agent and host cell during the earliest stages of host cell-pathogen interaction. We have developed in vitro assays for quantification of physiologically-relevant microbial adhesion as well as in vivo intestinal xenograft systems for testing the therapeutic efficacy of identified receptors or receptor analogues. Using this approach we identified a intestinal ganglioside receptor for porcine rotavirus and synthesized a neoglycolipid receptor mimetic that can function as a nutriceutical capable of blocking both virus binding and infectivity of host cells in vitro and virus shedding and diarrhea in vivo. We also are involved in collaborative basic and translational research studies aimed at identifying and delivering naturally occurring or synthetic inhibitors of apicomplexan parasites, particularly Cryptosporidium, in efforts to provide new approaches for the treatment of enteric parasitic disease in animals and people that are not readily amenable to traditional vaccine approaches. Our studies on cancer cell metastasis are aimed at understanding the mechanism by which the mechanical microenviroment of the primary tumor regulates cancer cell-cell adhesion and metastasis. Cancer deaths are primarily caused by metastasis, not the primary tumor. Cancer cells sense, process, and respond to mechanical signals, such as the degree of softness of their surrounding tissue, by regulating cell adhesion molecules and associated signal transduction processes. In collaborative studies with the Department of Mechanical Science and Engineering, we have discovered HCT-8 colon cancer cells develop an in vitro metastasis-like phenotype only when exposed to substrates resembling the stiffness range of target organs such as the liver, but not when exposed to conventional tissue culture plastic surfaces. This new finding suggests the onset of metastasis may occur, in part, through mechanosensing regulation of cell adhesion receptors and provides a new paradigm for exploration of novel drugs for the treatment of metastatic cancer.
Other Campus Affiliations
- Professor, Division of Nutritional Sciences
- Affiliate Professor, Agricultural and Biological Engineering
- Regulation of cancer metastasis by mechanical force, NSF (Role: Co-PI)
- A nanomechanical approach to understanding metastasis through cell adhesion measurement, NSF, (Role: Co-PI)
- Mechansims by which human milk oligosaccharides protect against rotavirus, NIH, (Role: Co-PI)
- Designing Selective Inhibitors of Calcium-Dependent Kinases in Parasites, Mark S. Kuhlenschmidt, NIH (PI, University of Illinois subaward)
- Targeting the double-stranded RNA viral symbiont of Cryptosporidium parvum,NIH – MCRE for Biodefense and Emerging Infectious Diseases; Mark S. Kuhlenschmidt (PI, University of Illinois Subaward)
- A continuous in vitro culture system for Cryptosporidium. Gates Foundation Grand Challenge, Mark S. Kuhlenschmidt (PI University of Illinois subaward)
- A continuous in vitro culture system for Cryptosporidium. Gates Foundation Phase II, Mark S. Kuhlenschmidt (PI University of Illinois subaward)
- Tang, X, Kuhlenschmidt TB, Zhou J, Bell P, Wang F, Saif TA, and Kuhlenschmidt MS (2010) Mechanical Force Affects Expression of an In Vitro Metastasis-Like Phenotype in HCT-8 Cells. Biophysical journal 99:2460-2469
- Bhattrai R, Kalita P, Trask J, Kuhlenschmidt MS (2011) Development of a physically-based model for transport of Cryptosporidium parvum in overland flow. Environ Modell SoftW 26:1289-1287.
- Bergner DW, Kuhlenschmidt TB, Firkins LD, and Kuhlenschmidt MS, (2011) Synthesis and characterization of a neoglycolipid that blocks porcine group A rotavirus infectivity Nutrients 3:228-244
- Liu Y, Kuhlenschmidt, MS, Kuhlenschmidt, TB, and Nguyen, TH. (2011) Characterization of Cryptosporidium parvum Oocyst Wall Macromolecules and Adhesion Kinetics of Oocysts on Quartz Surface. Biomacromolecules. 11:2109-15
- Tang X, Wen Q, Kuhlenschmidt TB, Kuhlenschmidt MS, Janmey PA, Saif TA (2012) Attenuation of Cell Mechanosensitivity in Colon Cancer Cells during In Vitro Metastasis. PLOS ONE 7 (11), e50443
- Davidson PC, Kuhlenschmidt TB, Bhattarai R, Kalita PC, Kuhlenschmidt MS (2013) Investigation of Rotavirus Survival in Different Soil Fractions and Temperature Conditions. Journal of Environmental Protection 4: 1-9
- Fate of Cryptosporidium parvum oocysts within soil, water, and plant environment. McLaughlin SJ, Kalita PK, Kuhlenschmidt MS.J Environ Manage. 2013 Dec 15;131:121-8. doi: 10.1016/j.jenvman.2013.09.017. Epub 2013 Oct 22.
- Fuller KL, Kuhlenschmidt TB, Kuhlenschmidt MS, Jimenez-Flores R, and Donovan SM. (2013) Milk Fat Globule Membrane Isolated from Buttermilk or Cheese Whey and their Lipid Component Inhibit Infectivity of Rotavirus In Vitro. J. Dairy Science 96(6):3488-97
- Liu, Y.Zhang, C.Hu, D.Kuhlenschmidt, M. S.Kuhlenschmidt, T. B.Mylon, S. E.Kong, R.Bhargava, R.Nguyen, T. H. (2013) Role of collector alternating charged patches on transport of Cryptosporidium parvum oocysts in a patchwise charged heterogeneous micromodel. Environ Sci Technol 47 2670-8
- Li M, Monaco MH, Wang M, Comstock SS, Kuhlenschmidt TB, Fahey GC Jr, Miller MJ, Kuhlenschmidt MS, Donovan SM.ISME J. (2014) Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota. (8):1609-20. doi: 10.1038/ismej.2014.10. Epub 2014 Feb 13.
- Davidson PC, Kuhlenschmidt TB, Bhattarai R,. Kalita PK, Kuhlenschmidt MS (2014) Effects of Soil Type and Cover Condition on Cryptosporidium parvum Transport in Overland Flow. Water, Air, & Soil Pollution 225:1882.
- A mechanically-induced colon cancer cell population shows increased metastatic potential. Tang X, Kuhlenschmidt TB, Li Q, Ali S, Lezmi S, Chen H, Pires-Alves M, Laegreid WW, Saif TA, Kuhlenschmidt MS. (2014) Mol Cancer. 13:131.
- Kuhlenschmidt, TB. Rutaganira, FU, Long, S, Tang, K, Shokat, K, M.Kuhlenschmidt, M, Sibley, LD. (2016) Inhibition of Calcium-Dependent Protein Kinase 1 (CDPK1) In Vitro by Pyrazolopyrimidine Derivatives Does Not Correlate with Sensitivity of Cryptosporidium parvum Growth in Cell Culture. Antimicrob Agents Chemother 60:57
- Comstock, SS. Li, M. Wang, M. Monaco, MH, Kuhlenschmidt, TB. Kuhlenschmidt, MS. Donovan, SM. (2017) Dietary Human Milk Oligosaccharides but Not Prebiotic Oligosaccharides Increase Circulating Natural Killer Cell and Mesenteric Lymph Node Memory T Cell Populations in Noninfected and Rotavirus-Infected Neonatal Piglets, The Journal of Nutrition, 147: (6), 1041–1047, https://doi.org/10.3945/jn.116.243774
- Wilke G, Ravindran S, Funkhouser- Jones L, Barks J, Wang Q, VanDussen KL, Stappenbeck TS, Kuhlenschmidt TB, Kuhlenschmidt MS, Sibley LD. (2018) Monoclonal antibodies to intracellular stages of Cryptosporidium parvum define life cycle progression in vitro. mSphere 3:e00124-18. https://doi.org/10.1128/mSphere.00124-18.
- Wilke, G. Funkhouser-Jones, LJ., Wang, Y. Ravindran, S. Wang, Q. Beatty, WL. Baldridge, ML. VanDussen, KL. Shen, B. Kuhlenschmidt, MS. Kuhlenschmidt, TB. Witola, WH. Stappenbeck, TS. Sibley, LD. (2019)
A Stem-Cell-Derived Platform Enables Complete Cryptosporidium Development In Vitro and Genetic Tractability. Cell Host & Microbe 26:(1), 123-134.e8
Wilke, G. Funkhouser-Jones, LJ., Wang, Y. Ravindran, S. Wang, Q. Beatty, WL. Baldridge, ML. VanDussen, KL. Shen, B. Kuhlenschmidt, MS. Kuhlenschmidt, TB. Witola, WH. Stappenbeck, TS. Sibley, LD. (2019) Forward Genetics in Cryptosporidium Enabled by Complete in Vitro Development in Stem Cell-Derived Intestinal Epithelium. Available at SSRN: https://ssrn.com/abstract=3331307 or http://dx.doi.org/10.2139/ssrn.3331307
- Additional Publications
Honors and Awards
- NIH-USPHS Predoctoral Fellow
- Olive V. Levin Memorial Fellow of the Leukemia Society of America
- Sigma Xi
- Who's Who in Veterinary Science and Medicine
- Morris Animal Foundation Award for Outstanding Research
- Omega Tau Sigma Veterinary Honor Fraternity (Honorary Member)
- Phi Zeta National Veterinary Honor Society, (Honorary Member)
- University of Illinois, College of Veterinary Medicine Research Award
- University of Illinois Incomplete List of Teachers Ranked Excellent by their students
- Engineering Open House/Agricultural Engineering, First Place Award for Original Research
- University of Illinois, College of Veterinary Medicine All-Round Excellence Award
- American Society for Biochemistry and Molecular Biology
- American Society for Microbiology
- American Chemical Society
- Illinois State Veterinary Medical Association (Associate)