It is also cellular mechanics, a proper subject for-you guessed it-an engineer.
Konstantopoulos, who chairs the Whiting School’s Department of Chemical and Biomolecular Engineering, is best known for his work on the mechanics of circulating tumor cells (CTCs), the seed cells that break off from primary tumors and form metastatic tumors elsewhere-cancer’s usual cause of death.
After CTCs detach from the original tumor, they circulate through the blood and have to bind securely to blood vessel walls before migrating through those vessel walls into new organs. “Only a tiny fraction of CTCs make this journey successfully, in part because the stresses on them from fluid turbulence and immune cell receptors are so great,” Konstantopoulos says. These stresses, as well as the amazing gripping strength of the clawlike appendages with which CTCs can hook themselves to vessel-lining endothelial cells, are properties described by the fundamentals of engineering. “By understanding this fluid mechanical environment, we can start to think about ways of interfering with the process, thereby reducing the chance that a tumor will metastasize,” he says.
Konstantopoulos’ lab, replete with vented workbenches and pipette-wielding grad students, looks very much like a biology lab. His research colleagues are often from the biomedical sciences. “Dr. Konstantopoulos applies the power of engineering, down to the single cell and even the single molecule level, to gain new insights that are meaningfully moving the field of cell-cell adhesion forward,” says frequent collaborator Ronald L. Schnaar, a professor in the departments of Pharmacology and Neuroscience at Johns Hopkins School of Medicine.
Yet another focus of the Konstantopoulos lab is the cell type known as chondrocytes, which build and maintain the cartilage of joints. “With chondrocytes we’ve been able to show that the forces on cells can affect not only their adhesion and migration characteristics but also their internal signaling pathways,” Konstantopoulos says.
When a weight lifter suddenly snatches up a 300-pound barbell, or a linebacker crashes headlong into a wide receiver, the cartilage in the knees and shoulders and elbows and hips and all the other shock-absorbing places in the skeleton are suddenly hit with large forces. Enough of these hits can cause osteoarthritis, a condition in which chondrocytes die off and cartilage starts to break down.
Sudden compressions of joints create sudden flows of synovial fluid-the lubricant of joints-and those flows severely buffet chondrocytes on the cartilage surface. In a series of studies over the past six years, including one published last December in PLoS ONE, Konstantopoulos and his students have shown that fast flows of synovial fluid can cause cultured chondrocytes to exhibit a degenerative gene expression pattern very similar to that seen in osteoarthritis. “Even though this fluid-mechanical model is very simple, we can use it to do preliminary tests of possible therapeutic agents to combat osteoarthritis,” he says.
It might seem odd to find engineers roaming so far onto biologists’ traditional turf. But Konstantopoulos points out that biological systems such as the joints and blood vessels represent “exquisite feats of mechanical engineering-just not at the scale at which we’re used to working.”
Financial Structures That Won’t Fall Down
“Financial engineering” got such a bad rap during the economic crisis that some may know it only as a term of derision-as if “engineering” in a financial context were a self-evidently absurd and dangerous idea.
But the truth is that there are financial engineers. Over the past two decades they’ve been part of one of the fastest growing disciplines in the engineering world, and they offer the same robust methodologies and social value provided by traditional types of engineers. “A structural engineer designs buildings to account for foreseeable loads, and in the same way a financial engineer designs instruments to account for foreseeable financial risks,” says Daniel Naiman, professor and chair of the Whiting School’s Department of Applied Mathematics and Statistics (AMS)-home of Johns Hopkins’ financial engineers.
“One of the positive outcomes of the financial crisis is that reliable financial engineering models have become more important than ever,” says Tim Leung, an AMS assistant professor. “There’s also a better appreciation of how these models should and shouldn’t be used.”
Leung made his name in the field recently by helping companies, regulators, and ordinary workers gain a more sophisticated understanding of employee stock options (ESOs). Granting ESOs to employees, to give them a sense of a stake in their companies, has become very common-yet it’s a potentially thorny issue for corporate accountants and regulators. The liability an ESO represents on the books of the issuing company can’t be measured exactly because it depends on the vicissitudes of stock prices and the timing of employee cash-ins.
Leung has shown that old ESO-valuation models are usually inaccurate, because they fail to take into account the heightened risk perceptions of ESO-holding employees. “Employees tend to exercise their options earlier than they should,” says Leung. “They tend to be risk averse, and so they prefer to lock in a small gain before the stock price declines, or before they lose their job-because in some cases they lose their ESOs if they’re fired or quit.”
A new model developed by Leung and colleagues takes employee risk perceptions into account and is now commonly used by companies to satisfy accounting regulations. Leung also has shown recently, in the SIAM Journal on Control and Optimization, how employees can hedge some of this risk in the open market, making it easier for them to hold their ESOs for longer-potentially increasing the cost of the ESOs to companies but also increasing the period in which employees have a profit-sharing stake in their companies’ success.
Another high-flying financial engineer at the Whiting School is PhD candidate Peter Lin, who won second runner-up in a Morgan Stanley market analysis and modeling competition last December.
Lin’s competition entry was a new model to help investors hedge against changes in interest rates. “Traditional interest-rate models are often too specific, involving assumptions about investors’ risk preferences or market risk evaluations that aren’t firmly connected to the real world,” says Lin. “This new model is simpler because it accommodates real-world market information with fewer constraints.” Lin’s model not only gauges the risk of interest rate changes-a risk that is of supreme interest to bond-holding asset managers, especially managers of pension funds-but also outputs the appropriate price for derivatives that hedge against this risk.
And speaking of Morgan Stanley: Graduating electrical or mechanical engineers sometimes find themselves questioning their career choices and wishing that they could follow their money-minded classmates to high-paying Master-of-the-Universe jobs on Wall Street. Financial engineers don’t have this problem because the financial industry is where they are trained to work. Lin, for example, expects to head to Wall Street soon to work as a quantitative modeler, or “quant.” Leung, before doing his PhD, spent a year in Manhattan as a consultant to banks. “The interest rates that your local bank charges for, say, home mortgages are set by models like the ones I designed while I was there,” he says. “I’m hoping that my impact on the field will be bigger if I’m here in academia, but it’s nice to know that if I want to go back, I probably can.”
“Over the last 20 years, the growth in the industry’s demand for financial engineers has been explosive,” says David Audley, PhD ’72, a former hedge funder who still consults on Wall Street but now spends his time lecturing and directing the AMS Department’s master’s degree program in financial mathematics. “The demand leveled off during the economic crisis, but recently it started to pick up again, and we get lots of calls now from hedge funds and asset managers.”
Callouts:
“We aim to develop it to the point that a blind person can use it to quickly learn the difference between, say, a box of Cheerios and a box of Frosted Flakes.”
-Ralph Etienne-Cummings, Professor of Electrical and Computer Engineering
“By understanding the fluid mechanical environment, we can start to think about ways of interfering with the process, thereby reducing the chance that a tumor will metastasize.”
-Konstantinos Konstantopoulos
“One of the positive outcomes of the financial crisis is that reliable financial engineering models have become more important than ever.”
-Tim Leung