When it comes to running a successful metallomics lab, Keith MacRenaris, PhD, Associate Director of Science and Development in the Chemistry of Life Processes Institute’s Quantitative Bio-element Imaging Center (QBIC), is a rare find.
“It takes expertise in both biology and inorganic chemistry, along with a hefty dose of mechanical ability, to do his job,” says Sheila Judge, Research Professor and Senior Director for Research, Education and Administration at CLP.
During his first tenure at QBIC from 2011 – 2018, MacRenaris and faculty director Thomas O’Halloran won an impressive five out of five federal grants submitted.
“The team at CLP helped enormously by doing a lot of the heavy lifting. They understood how the grants work, how to write them and how to sell them. Everybody was pulling on the same end of the rope,” said MacRenaris. “It required a lot of time and effort by a lot of dedicated, intelligent people whom I’ve had the pleasure of working with for almost 10 years.”
The biggest of the grants, an $8.2 million National Institutes of Health high-end instrument grant, helped to launch the Resource for Quantitative Elemental Mapping for the Life Sciences at Northwestern last fall. MacRenaris now oversees the implementation of the high-end time-of-flight (TOF)-ICP-MS developed by Tofwerks, made possible by the grant, that will allow scientists to map the distribution of all the elements at one time in tissues and cells.
“The possibilities for what we can garner from this instrument are endless. It will open up new opportunities for nanoparticle synthesis and characterization, tissue distribution, and metallomics analysis,” says MacRenaris. “It will provide better information about characterizing nanoparticle formulations and tell us a lot about disease, the environment, evolution and ecology, ultimately providing us a greater understanding of how metals and biology interact on a molecular level.”
IBIS or Bust
MacRenaris first arrived at Northwestern in 2002 as a student in the Interdisciplinary Biological Sciences Graduate Program. Intent on becoming a biomedical researcher and honing his laboratory skills, he knew that he liked biology, but was curious about other areas as well.
“The IBIS program interested me because I could rotate through engineering and chemistry labs,” says MacRenaris.
A recent graduate from the University of Rochester, he had majored in cell and developmental biology and minored in chemistry.
In the summer of his first year at Northwestern, MacRenaris worked in the labs of two different CLP members Carole LaBonne, the Erastus Otis Haven Professor of Molecular Bioscience, and Thomas Meade, the Eileen M. Foell Professor of Cancer Research and Professor of Chemistry, Molecular Biosciences, Neurobiology, Biomedical Engineering and Radiology.
Core Moves
“Professor Meade had just come to the university and his lab was still being unboxed,” says MacRenaris. “I worked with a graduate student, Matthew Allen (current professor and department chair of chemistry at Wayne State University) who came with Meade from Caltech and we got along great. We did some innovative things with cells and gadolinium contrast agents which I thought was pretty fun, so I decided then that I wanted to join Meade’s lab.”
There, MacRenaris collaborated on several faculty projects that required him to synthesize, assess and improve the effectiveness of magnetic resonance imaging agents working primarily with gadolinium. Clinically approved contrast agents containing gadolinium are extremely useful in MR angiography to provide sharper background images of arteries and veins as well as measuring changes in blood flow. The tools of the trade included inductively coupled plasma mass spectrometry (ICP-MS), quantitative analysis and other techniques.
“It’s almost an engineering challenge where you try to come up with innovative strategies to get gadolinium into cells to improve labelling efficiency and targeting.”
The ‘smart’ contrast agents in Professor Meade’s lab provide scientists with tools to visualize not only anatomical changes, but also molecular changes which can lead to identifying diseases, such as cancer and Alzheimer’s, much earlier in disease progression.
“Once the cancer becomes large enough to visualize without contrast agents, it gets a lot more challenging to either surgically remove or treat with chemotherapy and/or radiation. Ultimately the cancer may have metastasized which leads to significantly worse prognoses.”
After earning his PhD in 2009, MacRenaris completed his post doc and was hired as a Research Associate and manager of optical imaging in the recently opened Center for Advanced Molecular Imaging, a Chemistry of Life Processes Institute– affiliated core facility headed by Meade. CAMI provides state-of-the-art in vivo imaging modalities that enable basic science researchers and clinicians to develop new tools to image disease states of cells and small animals and their responses to treatment.
When QBIC needed managing director in 2011 to head operations, MacRenaris stepped into the role. In 2014, he became a Research Assistant Professor in Molecular Biosciences. Four years later, he left Northwestern to explore the for-profit world. He worked as a field application engineer for Thermo Fisher Scientific and, later, for Berkeley Lights, Inc. (BLI). While at BLI, MacRenaris and a colleague co-authored a paper in Nature Medicine in conjunction with Vanderbilt University’s Vaccine Center. The paper focused on the identification of two antibodies using BLI’s Beacon system that contributed to the rapid deployment of AstraZeneca’s COVID-19 vaccine.
“That was a lot of fun, but gave me the itch to get back to research and development,” said MacRenaris.
In his encore role at QBIC, he may have finally found his element.
by Lisa La Vallee