(3y) Multiscale Modeling and Experiments to Investigate the Disease Dynamics and Develop Clinical Intervention

My primary research interest is in the area of systems biology, specifically, quantitative system pharmacology, systems biomedicine, and cancer systems biology. Biological processes exhibit dynamics over a wide range of interconnected spatial and temporal scales. The successful integration and investigation of biochemical and physiological properties at different scales will reward our society with improved healthcare and medical therapies. Multiscale modeling connects the behavior across a broader scale to address the physiological, chemical, and phenotypic changes from healthy to a disease state. The computational and statistical analysis of such models can identify the key biomarkers in the disease dynamics. It will give us a mechanistic understanding of the downstream processes and narrow the range for experimental studies. I am interested in modeling the signaling network in physiological and pathophysiological conditions, intervention with drug delivery, and how drugs will be distributed (pharmacokinetic) and act at different biological scales (pharmacodynamic) with clinical application. I will also perform and integrate complementary experimental techniques (cell culture, microscopy, flow cytometry, microfluidic device, western blot analysis) with mathematical modeling, and work in collaboration with the experimental laboratory for model validation.

During my Ph.D. with Dr. Dipak Barua at Missouri University of Science and Technology, I developed a mechanistic mathematical model for the cell population to advance our knowledge and understanding in the multitude of disease progression. I was part of a team that conceived an agent-based modeling software, called “ParCell”, to systematically transform a single-cell biochemical network model into a cell population model. I implemented Gillespie's direct method to model the single-cell reaction network and applied parallel computing to analyze the collective behavior of the cell population. The overarching goal was to investigate the coordinated behavior for multicellular communication in bacterial quorum sensing. In addition, I designed and performed experiments to investigate the motility and physiological properties of bacterial cells using microscopy and flow cytometry. I also developed a spatiotemporal modeling tool to study the effect of geometry, physiological properties, and interactions among diffusive molecules (e.g. ligand-receptor, enzyme-substrate) on cell signaling. The scalability and computational efficiency of the framework were optimized by grid-based parallelism and multi time frame observation. Furthermore, I performed a multiscale modeling study to investigate the effect of physiological properties on the penetration efficacy of drug delivery nanoparticles in tissue. This model was designed to incorporate 2D tissue architecture, cellular heterogeneity, advective-diffusive motion, particle size, particle cell interactions, and cellular uptake. I also designed and performed experiments on the distribution of nanoparticles of different sizes in tumor tissue using microfluidic devices and change the shape of the particles using stretching techniques to increase their penetration efficacy.

My postdoctoral work with Dr. Ashlee N. Ford Versypt at Oklahoma State University 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 the signaling network and modeling tissue damage. I developed a multi-compartment physiology-based pharmacokinetic model to track and quantify the effect of short-chain fatty acid butyrate in the gut-bone axis which contributes to bone formation via immune cells. I am currently developing a computational model for dysregulation of the renin-angiotensin system due to SARS-CoV-2 infection to investigate tissue damage, disease progression, and possible intervention.

In my research program, I aim to develop multiscale mechanistic models connecting different time and length scales to investigate the dynamics of physiological processes including cellular network, tissue to organ level transport of biomolecules, and the activity of immune cells. These models will be used to predict the disease dynamics, develop interventions, pharmacokinetics, and pharmacodynamics of drugs in the human body, and give insight into new experimental studies. The experimental section in my lab will focus on cell analysis, distribution of particles in tissue, and investigate the dynamics of single-cell and tissue in healthy and disease conditions. I am currently working with the experimental scientist for the model validation.

Selected publication

1. Islam, Mohammad Aminul, Satyaki Roy, Sajal Das, and Dipak Barua. “Multicellular models bridging intracellular signaling and gene transcription to population dynamics.” Processes 6, no. 11(2018):
2. Islam, Mohammad Aminul, Sutapa Barua, and Dipak Barua. “A multiscale modeling study of particle size effects on the tissue penetration efficacy of drug-delivery nanoparticles.” BMC Systems Biology 11.1 (2017):

Selected presentation

1. Give an introductory tutorial on stochastic methods and SimBiology in Dr. Ashlee N. Ford Versypt lab.
2. A scalable parallel framework for multicellular communication in bacterial quorum sensing. In International Conference on Bio-inspired Information and Communication, 2019.

Teaching Interests

I am interested in teaching the core courses in chemical engineering including transport phenomena, thermodynamics, process control, material and energy balance, mass transfer, and heat transfer. I will connect the course material with examples from medical and industrial applications to prepare the students for the next stage of their life. As I worked in collaboration with computer science, chemistry, biology, and nutritional science department, I am highly interested to develop new course material for the numerical, computational, and experimental approaches in systems biology.