Discovering and characterizing new candidate drug targets and therapeutics

The Multicellular Systems Engineering lab focuses on the systematic analysis of chemical and mechanical signaling at the tissue scale, including developing computational models of how cells self-organize into organs of the correct shape and size. We address these questions using experiments and modeling in systems cell and ex vivo organ model systems that are amenable to sophisticated genetic approaches, live imaging and in vivo drug screening studies. Our work is highly collaborative and interdisciplinary. 

Developing new strategies for treating aggressive cancers and degenerative tissue diseases requires investigating cell  and developmental biology with new quantitative approaches and greatly benefits from an engineering perspective. Probing in vivo animal systems with quantitative tools, data driven and mechanistic computational modeling and live-imaging is key to developing new approaches and methods for controlling cell growth and maintaining tissue homeostasis. 

A strong track record. We have developed and utilized preclinical in vivo genetic models of human diseases, including cancer and Down’s Syndrome. We have built a continuous track record of interdisciplinary and collaborative research utilizing a range of models of human diseases. This effort develops bridges to translate the fundamental studies in the fruit fly toward applications in human medicine. As one example, we are leveraging the fruit fly as an early preclinical screening platform. Genetic techniques in Drosophila enable the rapid and inexpensive manipulation of multiple genes to generate complex cancer genotypes. Thus, these cancer models effectively reveal fundamental aspects of human cancer genetics.

Awards, honors, special achievements:

• Since 2021, Co-PI of the new NSF-funded Emergent Mechanisms in Biology of Robustness Integration and Organization Institute (EMBRIO institute). 
• Invited Visiting scholar, Northwestern University, NSF-Simons Center for Quantitative Biology (2019)
• Michiana 40 under 40 award (2019)
• Editorial Board Member of Biophysical Journal

Selected references:

1. Soundarrajan, DK, Huizar, FJ, Paravitorghabeh, R, Robinett, T, Zartman, JJ From spikes to intercellular waves: Tuning intercellular calcium signaling dynamics modulates organ size control. PLOS Computational Biology, 2021 17(11), e1009543. PMID: 34723960. PMCID: PMC8601605.
2. Huizar, F, Soundarrajan, D, Paravitorghabeh, R, Zartman, J. Interplay between morphogen‐directed positional information systems and physiological signaling. Developmental Dynamics, 249(3), 328-341. 2020 PMID: 31794137; PMCID: PMC7328709.
3. Brodskiy PA, Wu Q, Soundarrajan DK, Huizar FJ, Chen J, Liang P, Narciso C, Levis MK, Arredondo-Walsh N, Chen DZ, Zartman JJ. Decoding Calcium Signaling Dynamics during Drosophila Wing Disc Development. Biophys J. 2019 Feb 19;116(4):725-740. PubMed PMID: 30704858; PubMed Central PMCID: PMC6382932.
4. Narciso C, Zartman J. Reverse-engineering organogenesis through feedback loops between model systems. Curr Opin Biotechnol. 2018 Aug;52:1-8. PubMed PMID: 29275226; PubMed Central PMCID: PMC6013317. 
5. Howe EN, Burnette MD, Justice ME, Schnepp PM, Hedrick V, Clancy JW, Guldner IH, Lamere AT, Li J, Aryal UK, D'Souza-Schorey C, Zartman JJ, Zhang S. Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth. Nat Commun. 2020 Jun 15;11(1):3017. doi: 10.1038/s41467-020-16832-2. PMID: 32541798; PMCID: PMC7295786.
6. Rodriguez KX, Howe EN, Bacher EP, Burnette M, Meloche JL, Meisel J, Schnepp P, Tan X, Chang M, Zartman J, Zhang S, Ashfeld BL. Combined Scaffold Evaluation and Systems-Level Transcriptome-Based Analysis for Accelerated Lead Optimization Reveals Ribosomal Targeting Spirooxindole Cyclopropanes. ChemMedChem. 2019 Sep 18;14(18):1653-1661. doi: 10.1002/cmdc.201900266. Epub 2019 Jul 1. PMID: 31140738; PMCID: PMC6750968.
7. Breuer EK, Fukushiro-Lopes D, Dalheim A, Burnette M, Zartman J, Kaja S, Wells C, Campo L, Curtis KJ, Romero-Moreno R, Littlepage LE, Niebur GL, Hoskins K, Nishimura MI, Gentile S. Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling. Cell Death Dis. 2019 Feb 21;10(3):180. doi: 10.1038/s41419-019-1429-0. PMID: 30792401; PMCID: PMC6385342.
8. Huizar FJ, Hill HM, Bacher EP, Eckert KE, Gulotty EM, Rodriguez KX, Tucker ZD, Banerjee M, Liu H, Wiest O, Zartman J, Ashfeld BL. Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System. ChemMedChem. 2022 Feb 16;17(4):e202100512. doi: 10.1002/cmdc.202100512. Epub 2022 Jan 27. PMID: 34994084.

Find more info on Dr. Zartman here.