ACMD Seminar: Systems modeling for effective therapeutic intervention in the tumor microenvironment

Anne Talkington
Department of Biomedical Engineering, University of Virginia

Tuesday, September 19, 2023, 3:00-4:00 PM ET (1:00-2:00 PM MT)

A video of this talk will be made available to NIST staff in the Math channel on NISTube, which is accessible from the NIST internal home page. It will be taken down from NISTube after 12 months at which point it can be requested by emailing the ACMD Seminar Chair.

Abstract: Despite recent advances in medicine, many standard-of-care therapies are less effective than would be predicted given preclinical research efforts. Additionally, many of these front-line therapies are poorly tolerated. In silico modeling provides us with a window to explore both reasons for treatment failure and proposed methods for improved treatment. Determining the most effective treatment for a patient or population presents a complex optimization problem across multiple scales. I will present an overview of two models that together highlight issues of drug delivery and drug targeting. First, I will discuss a physiologically-based pharmacokinetic model for the delivery of PEGylated drug carriers. Exploring the parameter space of this multi-compartment system through Latin Hypercube Sampling reveals the involvement of antibody interference in altering the drug’s biodistribution. Next, I will illustrate a model for intercellular communication in advanced melanoma patients receiving immune checkpoint blockade. This framework for developing a cellular-level dynamical system from genomic data elucidates the landscape of cellular state changes in responders and non-responders, pre- and post-treatment. Perturbing such a model can provide insight into potential complementary therapeutic strategies for improved treatment response. 

Bio: Dr. Anne Talkington’s research is focused on studying the mechanisms of interaction between tumor and immune cells, with the goal of understanding how these interactions correspond to treatment resistance in cancer.  She uses a combination of mathematical modeling and data-based methods to associate tumor-immune interaction networks with the characteristics of a patient's tumor.  She aims to understand interactions in the tumor microenvironment that could be better targeted to improve responsiveness to therapy, and thus, patient outcome. Prior to her current appointment at UVA, Dr. Talkington completed her MS in Applied Mathematics and PhD in Computational Biology as an NSF Graduate Research Fellow and P.E.O. Scholar at UNC Chapel Hill. Her doctoral research presented a combination of physiologically-based pharmacokinetic modeling and experimental techniques to study adverse responses to PEGylated therapeutics as a result of anti-PEG antibodies.  She previously worked on differential equation models for immunotherapies as an undergraduate at Duke University.

Host: Ryan Evans / Tony Kearsley

Note: This talk will be recorded to provide access to NIST staff and associates who could not be present to the time of the seminar. The recording will be made available in the Math channel on NISTube, which is accessible only on the NIST internal network. This recording could be released to the public through a Freedom of Information Act (FOIA) request. Do not discuss or visually present any sensitive (CUI/PII/BII) material. Ensure that no inappropriate material or any minors are contained within the background of any recording. (To facilitate this, we request that cameras of attendees are muted except when asking questions.)

Note: Visitors from outside NIST must contact Lochi Orr at least 24 hours in advance.