Power Hungry Performance

Bioengineering’s most recent hire targets cell behavior to understand critical health concerns


By Ashley R. Smith

The tissues and organs in the body aren’t just influenced by nutrients and blood flow, but by changes in internal pressure, strain and stresses. All of these add up to create a dynamic environment that challenges biomedical researchers.

“Problems in human health have always been the most interesting to try to solve,” says Gretchen Mahler, assistant professor of bioengineering. Her research looks at how biochemical signals and biomechanical forces influence the building blocks of our body during the development and progression of disease or in response to therapeutic drugs or chemicals. “Does the shear flow over an epithelial layer cause changes around a tumor, and can it cause the tumor to metastasize or trigger further genetic changes in the tumor that lead it to mutate more?” It’s the kind of question that Mahler has been working to answer for the better part of a decade.

Mahler joined the Watson School faculty in fall 2011. Her specialty is in vitro cell-culture models of organs and tissues — a tool that mimics what is happening in the body.

Her peanut-sized “body-on-a-chip” has chambers of living cells etched onto silicon. Liquids containing drugs are passed through tiny channels to determine how they interact with and are absorbed by human kidney, liver, bone marrow, lung and tumor cells.

This three-dimensional dynamic-culture environment is a biomedical niche with the potential to shed new light on disease.

In vivo (in the body) experiments — such as animal testing — provide the most accurate data on how a compound interacts with an organism. But, Mahler says, it’s difficult and sometimes impossible to tell how the compound interacts with individual organs, tissues and cells.

In silico (computational) methods provide a great deal of data on how a drug or toxin interacts with a human, but, she explains, “the model’s performance and biological relevance depend greatly on the accuracy of the parameters you put into the model.”

In vitro testing is the middle ground. It can replicate some of the cell-to-cell interactions that are not as easily studied in vivo or in silico. And the data collected in vitro can be applied to computational models to improve accuracy. Mahler’s “body-on-a-chip” microfluidic device is the groundwork for better compact modeling of human systems.

“By taking things and shrinking them, we use less reagent, which lowers the expense and enables us to do more testing, and more at one time,” Mahler says. “It also brings it to a physiological scale that’s more realistic in cell-to-fluid ratios.”

Though new to Binghamton, Mahler has an impressive toolbox of skills when it comes to bioengineering or biomedical engineering. As a Cornell graduate student she worked in microfabrication, microscopy and computer modeling. As a postdoc she moved on to microbiological techniques, microsurgery, and primary cell isolation and culture. Her studies ranged from nutrient absorption, drug absorption and interaction of toxic substances such as nanoparticles in the gastrointestinal tract, to working to understand how biochemical signals and biomechanical forces influence heart valvulogenesis and the development of heart-valve disease.

Across the board, the common thread was building in vitro models.

At Binghamton, Mahler is collaborating with researchers on several projects that include studying the role of biomechanical and biochemical forces on the development of heart-valve disease; studying the role of biomechanical forces and biochemical factors on cancer-associated fibroblast generation and cancer progression; minimizing soybean allergies with natural engineering by studying soybean protein transport through models of the gastrointestinal tract; and investigating the pharmacokinetics of pHLIP — a novel anti-cancer peptide developed by Assistant Professor of Chemistry Ming An.

The pHLIP (pronounced “flip”) project targets tumors based on acidity in order to alleviate common issues with toxicity to surrounding healthy tissues. If successful, the team will have made major strides in selective drug delivery.

“When I went to college, I always had a medical slant and was thinking about being pre-med. But this is exactly where I want to be,” Mahler says. “Trying to solve problems in human health is not always specifically in the clinic.”

From the ground up

 

David Bassen and Assistnat Professor Gretchen Mahler

Bioengineering senior David Bassen began working with Mahler on tissue engineering last spring. He is interning for a second summer at the Wadsworth Center laboratories at the New York State Department of Health in Albany on an NSF Research Experience for Undergraduates supplemental grant. During his first internship at Wadsworth, Bassen examined molecular mechanics models, constructed a sequence alignment of intein structures and developed three-dimensional visualizations of the intein splicing mechanisms. This summer he is learning electron microscopy and extending his skills in computational modeling by characterizing microtubule-derived structures.


The Department of Bioengineering’s newest assistant professor, Gretchen Mahler, is quick to note that everything she needs to do her work, and to do it well, is here at Binghamton. That includes high-quality undergraduate and graduate students.

“The first year is a transition. I give students a list of projects I have available, they decide what they want to work on, and then they have to learn all the techniques in the lab,” Mahler says.

Bioengineering senior Matthew Reiss is one of eight to join her team. As an undergraduate research assistant, Reiss will grow and care for a stock of sensitive kidney cells necessary for cancer drug testing. To prepare, he received hands-on training from Mahler that ranged from laboratory safety techniques to how to make solutions and sterilize them, and then how to grow and work with cells.

“We got the whole spectrum of how you treat cells — everything from growing cells to cryogenically freezing them. We purposefully got to contaminate stuff so we could see what a bacterial infection looked like,” Reiss says. “We learned the basics of how it’s done, why it’s done and then practiced it.”

Bioengineering senior David Bassen is studying the interaction of therapeutic nanoparticles with heart-valve endothelial cells. Bassen is a Barry M. Goldwater Scholar.

Bioengineering junior Yehudah Pardo is working with cyanobacteria to develop biological solar cells.

Master of engineering student Qingfeng Cao is designing a microfluidic chamber for studying biological cell transformations.

Biomedical engineering master’s student Sara Mina is working with Cao to design and build a microfluidic chamber. Mina is also working with the endothelial and prostate cancer cells that will be grown and studied.

Biomedical engineering master’s student Frances Wallace is studying the absorption of soybean protein subunits through a model of the GI tract. The project will use natural plant enzymes to pre-digest soybean proteins with the hope that this pre-digestion will help minimize soybean allergies.

Biomedical engineering doctoral student Sudip Dahal is developing a microfluidic model of the heart valve to study the role of biochemical and biophysical factors on endothelial-to-mesenchymal transformation.

Biomedical engineering doctoral student Courtney Sakolish is developing a microfluidic device including kidney, liver, tumor and bone marrow cells to better understand the pharmacokinetics of pHLIP. Sakolish — a Clifford D. Clark Fellow — will develop and test two structures to grow an in vitro kidney most effectively.


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