Khaled Machaca, professor of physiology and biophysics at Weill Cornell Medicine and associate dean of research at Weill Cornell Medicine Qatar, grew up in Beirut, Lebanon, with a successful homemaker mother and a father who was the director of commercial traffic at the Port of Beirut. Growing up, he did not have a particular passion for science or any real idea of what career he planned to pursue, but he always enjoyed the sciences in school more than writing, and he liked tinkering and fixing things in his spare time.

He earned his bachelor’s degree in agriculture engineering from the American University of Beirut. “I had no intentions then to be involved in research as I was not familiar with what that would entail. Nonetheless, I was interested in pursu­ing graduate school out of a pure sense of seeking a better understanding of the science underlying approaches in the agriculture industry,” Machaca shares. “I chose to pursue an MS degree in Poultry Science [at the University of Georgia in Athens] with the thinking that this was a robust industry in Lebanon to pursue a career in.”

Looking to make some money with a graduate assistantship, he was offered a research assistant position where he worked on biochemical mechanisms governing cell death. “The rest is history, as they say. I quickly developed a passion for research as a career path. So, after the completion of my MS studies I pursued a PhD in cell and developmental biology at Emory University,” he says. “At Emory I chose to work on the genet­ic mechanisms controlling C. elegans spermatogenesis and spermiogenesis. However, I realized quickly that although ge­netic approaches are extremely powerful, especially in model organisms like C. elegans, they were too slow for my taste as I needed more immediate feedback.” He combined the genetic approach with electrophysiological recordings on C. elegans sperm using the patch clamp technique, in the first patching experiments on sperm. “That was my first exposure to bio­physics. The ability to tweak and control experiments in real time was very appealing and made me switch my focus to the regulation of ionic currents in cellular physiology,” he shares.

Following completion of his PhD, Machaca pursued his post­doctoral work in the lab of Criss Hartzell at Emory, focusing on the role and regulation of Ca2+-activated Cl channels in the frog oocyte using Xenopus laevis as a model system. He then established his own lab as an assistant professor at the University of Arkansas for Medical Sciences.

“I’ve had a long-standing interest in animal reproduction and gamete biology as early as my undergraduate days. Having done my PhD studies on the amoeboid worm sperm, I later focused on oocyte maturation, and in particular the regulation of Ca2+ signaling pathways during this cellular differentiation pathway,” he explains. “When I started my own lab I was fas­cinated by the fact that Ca2+ has been conserved throughout phylogeny as the signal that initiates egg activation and as such triggers organismal development through the egg-to-embryo transition. Hence, a Ca2+ rise at fertilization provides the spark of life to initiate development. Nonetheless, the fully grown oocyte in the ovary is unable to respond properly to sperm or trigger egg activation. It requires a differentiation period know as oocyte maturation during which many signal­ing and morphological processes remodel in preparation for fertilization and embryonic development.”

Machaca is now professor of physiology and biophysics at Weill Cornell Medicine and associate dean of research at Weill Cornell Medicine Qatar. When he moved to Qatar nearly a decade ago, there was very little scientific research estab­lished in the country. “We truly started that effort from the ground up. Contrary to the current situation, the research enterprise nationally in Qatar was practically non-existent at the time,” he shares. “The leadership in Qatar had an excep­tional vision driven by the Qatar Foundation to establish a research enterprise nationally, with the goal of transitioning away from an economy built solely on fossil fuels towards a knowledge-based economy.”

Currently, his lab is focused on four broad areas: (1) Non-genomic signaling downstream of the membrane progesterone receptor, (2) regulation of store-operated Ca2+ entry (SOCE) during the cellular differentiation, (3) role of Ca2+ signaling in cancer metastasis, and (4) Ca2+ tunneling. He hopes to continue with discoveries in the lab that would advance un­derstanding of cellular signaling in general and Ca2+ signaling in particular. In a broader sense, and through both his own lab and his role as an administrator, Machaca hopes to “make an impact on the national and institutional research efforts, particularly in terms of trans­lating discoveries in the lab toward clinically actionable efforts targeted at improving the health of individuals,” he shares.

“Balancing a dual role as an academic ad­ministrator in my role as associate dean for research while maintaining an active lab was initially quite challenging,” he shares. “We are trained as scientists and yet success in that arena is rewarded by administrative roles where the approach and expertise needed are often diametrically opposed to what one needs in science. Furthermore, administrative roles are often coupled to significant time demands, which takes away from the lab. Sci­ence is a competitive undertaking, so balanc­ing the two demands can be challenging.”

He has dealt with this challenge by restruc­turing his lab to include senior colleagues who can both manage the research independent­ly and help the more junior lab members in terms of both day-to-day support and techni­cal training.

Raphael Courjaret joined Machaca’s lab in 2010 as a postdoc. “He needed an electrophysi­ologist on a project aimed at identifying the interactions between different TRP subunits in the Xenopus oocyte,” he explains. “After this we started studying IP3 signaling and chloride channels in the oocyte. It led us to focus our interest on how cells deliver intracellular calci­um coming from the extracellular space to dis­tant or isolated effectors. We are still working on it and are now expending our approach of calcium signaling to the context of non-com­municable disease such as diabetes.”

Despite Machaca’s many responsibilities in his dual role, Courjaret notes that he always man­ages to find time to discuss ongoing projects, help solve issues that arise in the lab, and provide guidance on research focus. “He is an enthusiastic researcher and we were allowed to investigate numerous ideas we had in the lab even when they meant going a little bit ‘off road,’” he says. “But he is also able to tell us when a project is going nowhere and needs to be stopped or refocused. It probably connects with the fact that we are starting a research community here [in Qatar] nearly from scratch and that we need to explore a lot during this development.”

 

“Focus on quality rather than quantity in your science, in the long term it always pays off."

-Machaca

Like most researchers who take on additional administrative roles, Machaca sees less of the bench, and takes advantage of any time he finds to perform experiments. “One evening, while the entire lab was gathering for a dinner, he started getting very nice signals from Xeno­pus oocytes expressing a channel of interest,” Courjaret shares. “The ionic currents were huge, with the promise of an exciting research project. We waited for him for a very long time and he skipped a large part of the dinner. The day after, we realized he spent his evening recording cells expressing the wrong channel. Nobody got fired.”

When he is not working, he fills his time with exercise, fishing, and quality time with his family. He also enjoys experimenting with different cuisines.

Machaca’s career advice for young biophys­icists? Have fun. “Science is demanding and challenging and if you don’t particularly enjoy it there is little reason to pursue a career in science,” he says. “Focus on quality rather than quantity in your science, in the long term it always pays off. Rigor in your science is a priority especially with the variety of advanced techniques and plethora of publishing venues these days.”