(2eq) Engineering Models and Experiments in Gut-Lung Axis: Immunity Against Viral Infection and Foodborne Nanotoxicity

The central aim of my proposed research lab is to modulate the interactions between microbiota and immune cells in the gut-lung axis to develop treatments for viral infections and foodborne nanotoxicity. My research program will combine my expertise in modeling and experiments with my knowledge of process engineering to connect broader scales of biological processes and solve clinically relevant problems. I will complement the domain of systems biology and multiscale modeling with experiments to investigate the physiological and chemical processes that influence the local and systemic interactions among microbiota, immune cells, viruses, and nanomaterials. I will perform and integrate complementary experimental techniques, i.e., cell culture, microscopy, flow cytometry, and microfluidics, with mathematical modeling. I will also collaborate with other labs to collect experimental data at a wide range of biological scales for model validation.

My research area focuses on intracellular biochemical networks to organ scale behavior. My primary projects will address the followings:

1. Identify the local and systemic mechanisms of probiotics and bacterial metabolites in antiviral immunity in the gut-lung axis
2. Determine the impact of physicochemical properties of foodborne nanoparticles on probiotic nanotoxicity in the gut and their systemic effects on immune cells in the gut-lung axis

The long-term goal of my first project is to contribute to the development of better antiviral vaccines and preventive treatments that target the microbiome and host immune response. My overall objective is to identify the mechanisms and quantify the key factors of probiotics and bacterial metabolites that modulate the balance in inflammation to clear the influenza virus. I will quantify the effect of pro-and anti-inflammatory factors from probiotics and bacterial metabolites that reduce the infectivity of influenza infection in the gut-lung axis. I will also identify the compositions, dosage, timepoint, and duration of probiotics and bacterial metabolites for successful clearance of influenza virus.

The long-term goal of my second project is to investigate the impact of foodborne inorganic nanomaterials on the gut microbiome-immune axis. My overall objective is to identify how the varying size and shape of silver nanoparticles (AgNPs) influence the toxicity and compositions of probiotics. Experiments on intestine-in-chip microfluidics can recreate the complex gut microbiota in intestinal structure. I will recreate gut microbiota in the intestine using similar techniques and observe the interactions between microbiome and AgNPs using microscopy. I will collect time-series data to identify the interaction dynamics, toxicity, and compositions of probiotics and develop predictive models. Similar experimental techniques will also be used for model validation in the first project.

My postdoctoral work with Prof. Ashlee N. Ford Versypt at Oklahoma State University and now the University at Buffalo, The State University of New York, has focused on the pharmacokinetics and pharmacodynamics of the drug molecules, computational modeling of the local and systemic immune response, identification, and intervention of the key biomarkers in signaling networks, and modeling tissue damage. I developed a multi-compartment physiology-based pharmacokinetic model to track and quantify the effect of the short-chain fatty acid butyrate in the gut-bone axis, which contributes to bone formation via immune cells. I am currently working on a coalition project with researchers from diverse backgrounds to develop an open-source, multiscale tissue simulator that can be used to investigate the mechanisms of intracellular viral replication, infection of lung epithelial cells, host immune response, and tissue damage during SARS-CoV-2 infection. I am integrating a computational model in the coalition project to study the role of stationary and mobile sources of TGF-β in the fibroblast-mediated collagen deposition at damaged sites of the infected tissue. In the extension of this model, I also investigated the effect of pre-morbidity, i.e., hypertension before SARS-CoV-2 infection, in the long-term fibrosis.

During my graduate training at the Missouri University of Science and Technology under the direction of Prof. Dipak Barua, I specialized in multiscale modeling of multicellular communication and nanomaterial therapeutics. I developed novel analytical, numerical, and computational methods to study the coordinated behavior for multicellular communication in bacterial quorum sensing and the effect of physiological properties on the penetration efficacy of nanoparticles in tissue. I also designed and performed experiments to investigate the motility and physiological properties of bacterial cells using microscopy and flow cytometry and the distribution of nanoparticles of different sizes in tumor tissue using microfluidic devices.

Selected Journal Publications

1. M. A. Islam, C. V. Cook, B. J. Smith, and A. N. Ford Versypt, “Mathematical modeling of the gut–bone axis and implications of butyrate treatment on osteoimmunology,” Ind. Eng. Chem. Res. vol. 60, no. 49, p. 17814-17825, 2021. DOI: 10.1021/acs.iecr.1c02949.
2. C. V. Cook, M. A. Islam, B. J. Smith, A. N. Ford Versypt, “Mathematical modeling of the effects of Wnt-10b on bone metabolism,” AIChE J. Accepted Author Manuscript e17809, 2021. DOI: 10.1002/aic.17809.
3. M. Getz, Y. Wang, G. An, A. Becker, C. Cockrell, N. Collier, M. Craig, C. L. Davis, J. Faeder, A. N. F. Versypt, J. F. Gianlupi, J. A. Glazier, S. Hamis, R. Heiland, T. Hillen, D. Hou, M. A. Islam, et al., “Iterative community-driven development of a SARS-CoV-2 tissue simulator,” bioRxiv preprint, 2021. DOI: 10.1101/2020.04.02.019075v4.
4. M. A. Islam, S. Roy, S. K. Das, and D. Barua, “Multicellular models bridging intracellular signaling and gene transcription to population dynamics,” Processes, vol. 6, no. 11, p. 217, 2018. DOI: 10.3390/pr6110217.
5. M. A. Islam, S. Barua, and D. Barua, “A multiscale modeling study of particle size effects on the tissue penetration efficacy of drug-delivery nanoparticles,” BMC Syst. Biol., vol. 11, no. 1, p. 113, 2017. DOI: 10.1186/s12918-017-0491-4.

Selected Conference Proceedings

1. S. Roy, M. A. Islam, S. Das, and D. Barua, “A scalable parallel framework for multicellular communication in bacterial quorum sensing,” In International Conference on Bio-inspired Information and Communication, 2019.

Teaching Interests

My teaching philosophy focuses on creating an environment to guide students from all backgrounds through intellectual development and promote their curiosity for lifelong learning. I am committed to inspiring my students with the motivation to become critical thinkers in the scientific process and endure the hard work to follow. My teaching strategy involves students understanding the fundamental concepts and helping them develop a rationale set of rules with critical thinking to solve diverse groups of problems. During my undergraduate, I mentored high school students, where I first explained to them the basic idea and then showed how, using the same idea, they can solve multiple problems. My goal is to promote the critical thinking of students by experimentation with general concepts and looking into different angles to solve divergent problems. In addition, I will include examples from my research lab in the course materials and promote students’ engagement and inclusion in my classroom.

I will create a learning environment to engage students in course materials, provide conceptual and technical training with tangible applications, and prepare them for future academic and career goals. I am interested in teaching the core courses in chemical engineering, including mass and heat transport, process control, reaction kinetics, and material and energy balances. I envision developing elective courses on biological transport, quantitative biology, quantitative computational science, and advanced numerical methods. My research interests, background, expertise, and collaborations with computer science, chemistry, biology, and nutritional science departments make me suited to develop these interdisciplinary, cutting-edge courses.