{{Short description|American chemist (born 1968)}} {{Infobox scientist | name = Milan Mrksich | image = | birth_date = {{Birth date and age|1968|08|15}} | birth_place = Chicago, Illinois | education = University of Illinois at Urbana-Champaign (BS) <br>California Institute of Technology (PhD) | known_for = SAMDI-MS Biochip Technology, Megamolecules | title = {{Unbulleted list|Vice President for Research|Henry Wade Rogers Professor of Biomedical Engineering at Northwestern University}} | awards = {{Unbulleted list|Camille Dreyfus Teacher-Scholar Award|TR100 Innovator Award|Arthur C. Cope Scholar Award|American Institute for Medical and Biological Engineering|Illinois Bio ICON Innovator Awardee}} | fields = {{Unbulleted list|Chemistry|Biomedical Engineering|Cell Biology}} | workplaces = {{Unbulleted list|Harvard University|University of Chicago|Northwestern University}} | website = {{URL|https://www.mrksichgroup.northwestern.edu/|Mrksich Group}} }}
'''Milan Mrksich''' (born 15 August 1968) is an American chemist. He is the Henry Wade Rogers Professor at Northwestern University with appointments in chemistry, biomedical engineering and cell & developmental biology.<ref>{{cite web |url=https://www.mccormick.northwestern.edu/research-faculty/directory/profiles/mrksich-milan.html |title= Professor Milan Mrksich |author = Northwestern University |publisher = McCormick School of Engineering}}</ref> He also served as both the founding director of the Center for Synthetic Biology and as an associate director of the Robert H. Lurie Comprehensive Cancer Center at Northwestern.<ref>{{cite web |url=https://syntheticbiology.northwestern.edu/people/faculty.html |title= Center for Synthetic Biology |author = Northwestern University}}</ref><ref>{{cite web |url=https://www.cancer.northwestern.edu/about/leadership/index.html |title= Robert H. Lurie Comprehensive Cancer Center of Northwestern University |author = Northwestern University |publisher = Feinberg School of Medicine}}</ref> Mrksich also served as the Vice President for Research of Northwestern University.<ref>{{Cite web|url=https://news.northwestern.edu/stories/2020/05/milan-mrksich|title=Milan Mrksich named Northwestern's Vice President for Research|last=Samuelson|first=Kristin|date=2020|website=Northwestern Now}}</ref>
His research involves the chemistry and synthesis of surfaces that contact biological environments. His laboratory has pioneered several technologies, including strategies to integrate living cells with microelectronic devices, methods to enable high throughput assays for drug discovery, and approaches to making synthetic fusion proteins for applications as therapeutics. Most notably, he developed the SAMDI-MS biochip technology that allows for high-throughput quantification of surface-based biochemical assays using MALDI mass spectrometry. Through SAMDI-MS, Mrksich has become a leader in using label-free technology for drug discovery, founding the company SAMDI Tech in 2011 that primarily serves global pharmaceutical companies.<ref>{{cite web |url=https://www.samditech.com/about-samdi-tech/ |title= About SAMDI Tech |author = SAMDI Tech}}</ref> His work has been described in over 240 publications (h-index 98), 500 invited talks, and 18 patents.<ref>{{cite web |url=https://scholar.google.com/citations?hl=en&user=kepuEw8AAAAJ&view_op=list_works&sortby=pubdate |title= Milan Mrksich Publishing Record |author = Google Scholar}}</ref>
== Early life and education == Milan Mrksich ({{lang-sr-Cyrl|Милан Мркшић}}{{citation needed|date=July 2022}}) was born on August 15, 1968, to Serbian immigrants and raised in Justice, Illinois.<ref>{{Cite web|url=https://www.chicagobusiness.com/article/20140717/ISSUE01/140719916/how-mrksich-s-samdi-tech-can-screen-100-000-drug-compounds-a-day-for-pharma-research|title = This drug-testing lab is speed-of-light fast|date = 16 July 2014}}</ref> He graduated from University of Illinois at Urbana-Champaign in 1989 with a B.S. in chemistry working in the laboratory of Steven Zimmerman on molecular tweezers. He completed his PhD in organic chemistry in 1994 from Caltech under chemist Peter B. Dervan. After graduate school, he was an American Chemical Society postdoctoral fellow at Harvard University under chemist George M. Whitesides before joining the faculty at the University of Chicago in 1996. He worked there for 15 years before joining the faculty at Northwestern University in 2011.<ref>{{cite web |url=https://docs.house.gov/meetings/IF/IF17/20140729/102566/HMTG-113-IF17-Bio-MrkichM-20140729.pdf |title= Milan Mrksich Biographical Sketch |author = United States House of Representatives}}</ref>
== Research history == === Early career === Early on as an independent investigator, Mrksich developed and executed the concept of ''dynamic substrates'' for cell culture. Here, self-assembled monolayers (SAMs) present cell adhesive ligands with perfect control over density and orientation against a non-adhesive, inert background, such as ethylene glycol. These monolayers can be further modified with electroactive groups that selectively release immobilized ligand when stimulated with an electric potential. Several strategies using this approach were studied in the context of cell signaling, migration, and co-culture.<ref>{{cite journal |last1=Yousaf |first1=M.N. |last2=Houseman |first2=B.T. |last3=Mrksich |first3=M. |year= 2001 |title=Turning on Cell Migration with Electroactive Substrates |journal=Angew. Chem. Int. Ed. |volume=40 |issue=6 |pages= 1093–1096 |doi=10.1002/1521-3773(20010316)40:6<1093::aid-anie10930>3.3.co;2-h}}</ref><ref>{{cite journal |last1=Hodneland |first1=C.D. |last2=Mrksich |first2=M. |year= 2000 |title=Biomolecular Surfaces that Release Ligands Under Electrochemical Control |journal=J. Am. Chem. Soc. |volume=122 |issue=17 |pages= 4235–4236 |doi=10.1021/ja000419p|bibcode=2000JAChS.122.4235H }}</ref><ref>{{cite journal |last1=Yousaf |first1=M.N. |last2=Houseman |first2=B.T. |last3=Mrksich |first3=M. |year= 2001 |title=Using Electroactive Substrates to Pattern the Attachment of Two Different Cell Types |journal=Proc. Natl. Acad. Sci. |volume=98 |issue=11 |pages= 5992–5996 |doi=10.1073/pnas.101112898|pmid=11353818 |pmc=33411 |doi-access=free }}</ref> Subsequent cell-based work focused on developing methods to pattern cells on the aforementioned SAMs. The work has mostly utilized microcontact printing to confine adherent cells into defined positions, shapes, and sizes. Ultimately, his group's work has revealed examples of how cellular mechanics and cytoskeletal structure influence phenotype. A primary example of this involved investigating how cell shape exerts control over the differentiation of mesenchymal stem cells.<ref>{{cite journal |last1=Kilian |first1=K.A. |last2=Bugarija |first2=B. |last3=Lahn |first3=B.T. |last4=Mrksich |first4=M. |year= 2001 |title=Geometric Cues for Directing the Differentiation of Mesenchymal Stem Cells |journal=Proc. Natl. Acad. Sci. |volume=107 |issue=11 |pages= 4872–4877 |doi=10.1073/pnas.0903269107 |pmid=20194780 |pmc=2841932 |doi-access=free }}</ref> Further work utilized these patterned monolayers to investigate the relationship between various cytoskeletal elements and to observe complex phenotypic differences in patient-derived neuroprogenitor cells.<ref>{{cite journal |last1=Shabbir |first1=S.H. |last2=Cleland |first2=R.D. |last3=Goldman |first3=R.D. |last4=Mrksich |first4=M. |year= 2014 |title=Geometric Control of Cytoskeletal Elements: Impact on Vimentin Intermediate Filaments |journal=Biomaterials |volume=35 |issue=5 |pages= 1359–1366 |doi=10.1016/j.biomaterials.2013.10.008|pmc=3875369 |pmid=24268665 }}</ref><ref>{{cite journal |last1=Brennand |first1=J.N. |last2=et |first2=al. |year= 2014 |title=Geometric Control of Cytoskeletal Elements: Impact on Vimentin Intermediate Filaments |journal=Mol. Psych. |pages= 1–8}}</ref> Recent work in the group investigating cell patterning has utilized ''photo''active adhesive peptides, allowing for local, spatiotemporal control of cell adhesion to study gap junction formation.<ref>{{cite journal |last1=Bugga |first1=P. |last2=Mrksich |first2=M. |year= 2019 |title=Sequential Photoactivation of Self-Assembled Monolayers to Direct Cell Adhesion and Migration |journal=Langmuir |volume=35 |issue=17 |pages= 5937–5943 |doi=10.1021/acs.langmuir.8b04203|pmid=30943037 |pmc=8262134 }}</ref>
=== SAMDI-MS ===
While performing much of the early dynamic substrate and cell patterning work, Mrksich also pioneered an assay platform that utilizes SAMs of alkanethiolates on gold.<ref>{{cite journal |last1=Houseman |first1=B.T. |last2=Huh |first2=J.H. |last3=Kron |first3=S.J. |last4=Mrksich |first4=M. |year= 2002 |title=Peptide Chips for the Evaluation of Protein Kinase Activity |journal=Nature Biotechnology |volume = 20 |issue=3 |pages= 270–274 |doi=10.1038/nbt0302-270|pmid=11875428 |s2cid=18043752 }}</ref><ref>{{cite journal |last1=Su |first1=J. |last2=Mrksich |first2=M. |year= 2002 |title=Using Mass Spectrometry to Characterize Self-Assembled Monolayers Presenting Peptides, Proteins and Carbohydrates |journal=Angew. Chem. Int. Ed. |volume = 41 |issue=24 |pages= 4715–4718 |doi=10.1002/anie.200290026|pmid=12481336 }}</ref> The monolayers contain capture ligands (e.g. biotin or maleimide) that can selectively immobilize a peptide of interest. Subsequently, the monolayer can treated with a specific enzyme or a complex mixture, such as cell lysate, that can modify the peptide through various biological processes (e.g. phosphorylation). For quality control, the monolayers present these peptides against a background of tri(ethylene glycol) groups to prevent the nonspecific adsorption of protein to the surface that could obfuscate the reaction signal and, therefore, enable quantitative and reproducible assays. Most significantly, the monolayers can be characterized with MALDI mass spectrometry in a technique known as SAMDI-MS, which provides the masses of the substituted alkanethiolates and, therefore, the mass change of the immobilized peptide that results from enzyme activity. The method is compatible with standard array formats and liquid handling robotics, allowing a throughput in the tens of thousands of reactions per day. Importantly, the matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF) analysis provides a fast and quantitative mass shift readout without the need for labels.
===Megamolecules=== Most recently, Mrksich's group has focused on developing a technique for assembling large molecular structures with perfectly defined structures and orientations, known as ''Megamolecules''. This is primarily done through use of fusion proteins and irreversible inhibitor linkers that assemble stable intermediates.<ref>{{cite journal |last1=Modica |first1=J.A. |last2=Skarpathiotis |first2=S. |last3=Mrksich |first3=M. |year= 2012 |title=Modular Assembly of Protein Building Blocks to Create Precisely-Defined MegaMolecules |journal=ChemBioChem |volume = 13 |issue=16 |pages= 2331–2334 |doi=10.1002/cbic.201200501|pmid=23070998 |pmc=3804166 }}</ref> Structure-function relationships, including synthesis of cyclic and antibody-mimic structures have been investigated for potential therapeutic application.<ref>{{cite journal |last1=Modica |first1=J.A. |last2=Lin |first2=Y. |last3=Mrksich |first3=M. |year= 2018 |title=Synthesis of Cyclic Megamolecules |journal=J. Am. Chem. Soc. |volume = 140 |issue=20 |pages= 6391–6399 |doi=10.1021/jacs.8b02665|pmid=29723476 |bibcode=2018JAChS.140.6391M |s2cid=13688765 }}</ref><ref>{{cite journal |last1=Taylor |first1=E.L. |last2=Metcalf |first2=K.J. |last3=Carlotti |first3=B. |last4=Lai |first4=C.-T. |last5=Modica |first5=J.A. |last6=Schatz |first6=G.C. |last7=Mrksich |first7=M. |last8=Goodson |first8=T. |year= 2018 |title=Long-Range Energy Transfer in Protein Megamolecules |journal=J. Am. Chem. Soc. |volume = 140 |issue=46 |pages= 15731–15743 |doi=10.1021/jacs.8b08208|pmc=6710013 |pmid=30375862 |bibcode=2018JAChS.14015731T }}</ref>
== Entrepreneurship == Mrksich has been an active entrepreneur over the past twenty years. He co-founded SAMDI Tech in 2011, which uses his label-free assay technology to perform high throughput screens for pharmaceutical companies. SAMDI Tech entered into a partnership with Charles River Laboratories in 2018 and was purchased by CRL in 2023.<ref>{{Cite web |title=Charles River Expands Strategic Partnership With SAMDI Tech {{!}} Charles River Laboratories International, Inc. |url=https://www.samditech.com/about-samdi-tech/news/charles-river-laboratories-acquires-samdi-tech/ |access-date=2022-05-25 |website=ir.criver.com |language=en}}</ref><ref>{{Cite web |date=2023-01-30 |title=Drug discovery startup spun out of Northwestern acquired for $50 million |url=https://www.chicagobusiness.com/health-care/northwestern-drug-discovery-startup-samdi-tech-acquired-50-million |access-date=2023-02-10 |website=Crain's Chicago Business |language=en-US}}</ref> Mrksich also co-founded WMR Biomedical in 2008, with George Whitesides and Carmichael Roberts to develop resorbable stent materials; this company was renamed Lyra Therapeutics and had an IPO in 2020 (NASDAQ LYRA) and has drug-eluting stents in clinical trials for ear, nose and throat disease, including chronic rhinosinusitis.<ref>{{Cite web |date=2020-05-01 |title=Lyra Therapeutics Announces Pricing of Initial Public Offering |url=https://www.businesswire.com/news/home/20200430006078/en/Lyra-Therapeutics-Announces-Pricing-of-Initial-Public-Offering |access-date=2022-05-25 |website=www.businesswire.com |language=en}}</ref> Mrksich has recently founded ModuMab Therapeutics, which applies his megamolecule technology to creating antibody mimics for a broad range of diseases.
== Service == Mrksich has also been active in serving the scientific community in a number of roles. These include his current service as the Scientific Director<ref>{{Cite web |date=2022-06-09 |title=Advisory Council |url=https://searlescholars.org/advisory-council/ |access-date=2022-09-20 |language=en}}</ref> of the Searle Scholars Program, as a member of the Board of Governors<ref>{{Cite web |title=Board of Governors {{!}} UChicago Argonne LLC |url=https://www.uchicagoargonnellc.org/board-governors |access-date=2022-09-20 |website=www.uchicagoargonnellc.org}}</ref> for Argonne National Laboratory, and as a member of the Board of Directors<ref>{{Cite web |title=About Us |url=https://www.dreyfus.org/about-us/ |access-date=2022-09-20 |website=Dreyfus Foundation |language=en-US}}</ref> for the Camille & Henry Dreyfus Foundation. His past appointments include service and chairing DARPA’s Defense Sciences Research Council and many program advisory committees.
== Awards and honors == {{Bulleted list |1990 — National Institutes of Health National Research Service Award |1993 — Ralph M. Parsons Foundation Graduate Fellow |1994 — American Cancer Society Postdoctoral Fellow |1996 — Searle Scholar Award |1996 — Camille and Henry Dreyfus New Faculty Award |1996 — DARPA Defense Sciences Research Council (2004-, Vice-Chair) |1997 — Editorial Board of ''Langmuir'' |2000 — A.P. Sloan Research Fellow |2000 — Camille Dreyfus Teacher-Scholar |2000 — WTEC Panel for International Evaluation of Tissue Engineering Programs |2001 — Extramural Chair for NIH/BECON Symposium on Biosensors |2002 — TR100 Young Innovator Award |2002 — International Panel for Review of Materials Research in United Kingdom |2003 — Board of Governors for Argonne National Laboratory |2003 — American Chemical Society Arthur C. Cope Young Scholar Award |2004 — Advisory Board of the Searle Scholars Program (2007-present, Chair) |2004 — Editorial Board of Chemical Society Reviews |2004 — Editorial Board of Chemistry & Biology |2005 — Fellow, American Association for the Advancement of Science |2008 — Editorial Board of Small |2011 — Founder and Chairman, SAMDI Tech, Inc. |2013 — Fellow, American Institute for Medical and Biological Engineering (AIMBE) |2014 — Advisory Professor, Institute of Chemical Biology and Nanomedicine, Hunan University |2015 — Visiting Professor, Institute for Nanomedicine at NTU, Singapore |2016 — iBIO iCON Innovator Award |2020 — Pittsburgh Analytical Chemistry Award<ref>{{Cite web|url=https://www.uchicagoargonnellc.org/person/milan-mrksich|title = Awards and honors|date = 25 May 2022}}</ref>|2022 — Board of Directors, Camille & Henry Dreyfus Foundation<ref>{{Cite web|url=https://www.dreyfus.org/bao-and-mrksich-elected-to-board/|title = Mrksich elected to board|date = 26 May 2022}}</ref>}}
== Personal life == Milan lives in Hinsdale, Illinois with his two children.{{citation needed|date=May 2022}}
== References == {{Reflist}}
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{{DEFAULTSORT:Mrksich, Milan}} Category:American bioengineers Category:Scientists from Chicago Category:Northwestern University faculty Category:University of Illinois Urbana-Champaign alumni Category:California Institute of Technology alumni Category:American Chemical Society Category:University of Chicago faculty * Category:People from Hinsdale, Illinois Category:Living people Category:1968 births Category:American people of Serbian descent