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Current Research Projects

Adaptable modularity in cellular functions

A./ Bacterial chemotaxis

Long, Z., Quaife B, Salman, H., Oltvai, Z.N. (2017) Cell-cell communication enhances bacterial chemotaxis toward external attractants. Sci. Rep., 7:12855; PMID: 28993669 

  • highlighted in Curr. Opin. Microbiol.: PMID: 29453124 

Rashid, S., Long, Z., Singh, S., Kohram, M., Vashistha, H., Navlakha, S., Salman, H., Oltvai, Z.N, Bar-Joseph, Z., (2019) Adjustment in tumbling rates improves bacterial chemotaxis on obstacle-laden terrains. Proc. Natl. Acad. Sci. U.S.A., 116, 11770-11775; PMID: 31127043

  • highlighted in Nat. Rev. Microbiol.: PMID: 31182826   

B./ Cell metabolism

Singh, M., Warita, K., Warita, T., Faeder, J.R., Lee, R.E.C., Sant, S., Oltvai, Z.N. (2018) Shift from sto­chastic to spatially-ordered expression of serine-glycine synthesis enzymes in 3D microtumors. Sci. Rep., 8: 9388; PMID: 29925909 synopsys

2D-3DNetwork biology-based modeling of cell metabolism is constrained by the available ge­nomic and functional -omic data that have almost exclusively been collected using 2-dimensional (2D) monolayer or liquid cell cultures.  Yet, in reality, most cells exist as components of ecosystems in which they are re­spond­ing dynamically to a cacophony of temporally changing signals from their environ­ment and from other cells.  In this pa­per, we show that mono­clonal tumor cell 2D monolayers display a sto­chastic expression of PHGDH, the rate limiting enzyme of the serine-glycine synthesis path­way, that shift to a spatially-re­stricted expression pattern when the same monoclonal tumor cells are grown as 3D-micro­tumors. A mathematical model indi­cates that this expression pattern is an emergent property of this simple ecosystem, likely driven by intercellular paracrine signals from the hypoxic and relatively nutrient-deprived mi­crotumor core. This paper clearly illustrates that studying cells in a microenvironment that recapitulates their nat­ural ecosystem state is an essential requirement for future research on cell metabolism.

Delaying metastasis formation by synergistic inhibition of metabolic pathways

Warita, K., Warita, T., Beckwitt, C.H, Schurdak, M.E., Vazquez, A., Wells, A., Oltvai, Z.N., (2014) Statin-induced mevalonate pathway inhibition attenuates the growth of mesenchymal-like cancer cells that lack functional E-cadherin mediated cell cohesion. Sci. Rep., 4:7593, PMID: 25534349

Raghu, V., Beckwitt, C.H, Warita, K., Wells, A., Benos, P.V., Oltvai, Z.N., (2018) Biomarker identifica­tion for statin sensitivity of cancer cell lines. Biochem. Biophys. Res. Comm., 495: 659-665; PMID: 29146185

Beckwitt, C.H., Clark, A.M., Ma, B., Whaley, D., Oltvai, Z.N., Wells, A. (2018) Statins attenuate outgrowth of breast cancer metastases. Br. J. Cancer, 119, 1094–1105; PMID: 30401978

Ishikawa, T., Hosaka, Y.Z., Beckwitt, C.H., Wells, A., Oltvai, Z.N., Warita, K.  (2018) Concomitant attenuation of HMG-CoA reductase expression potentiates the cancer cell growth-inhibitory effect of statins and expands their efficacy in tumor cells with epithelial characteristics. Oncotarget, 9: 29304-29315; PMID: 30034619

Warita, K., Ishikawa, T., Sugiura, A., Tashiro, J., Shimakura, H., Hosaka, Y.Z., Ohta, K., Warita, T. and Oltvai, Z.N. (2021) Concomitant attenuation of HMGCR expression and activity enhances the growth inhibitory effect of atorvastatin on TGF-β-treated epithelial cancer cells. Sci. Rep., 11: 12763; PMID: 34140545

Methods for pathogenicity and targeted therapy resistance assessment of genomic variants

Ponzoni, L., Penaherrera, D.A., Oltvai, Z.N., Bahar, I. (2020) Rhapsody: Predicting the pathogenicity of human missense variants. Bioinformatics, 36, 3084-3092; PMID: 32101277

Oltvai, Z.N., Smith, E.A., Wiens, K., Nogee, L.M., Luquette, M., Nelson, A.C., Wikenheiser-Brokamp, K.A. (2020) Neonatal respiratory failure due to novel compound heterozygous mutations in the ABCA3 lipid transporter. Cold Spring Harb. Mol. Case Stud., 6:a005074; PMID: 32532878

Oltvai Z.N., Harley, S.E., Koes, D., Michel, S., Warlick, E.D., Nelson, A.C., Yohe, S. and Mroz, P (2021). Assessing acquired resistance to IDH1 inhibitor therapy by full exon IDH1 sequencing and structural modeling, Cold Spring Harb. Mol. Case Stud., 7:a006007, PMID: 33832922