Understanding growth trajectories in science: personal and neuronal
A conversation with graduate student Ivan J. Santiago
October 5, 2016
by Parizad Bilimoria
Ivan Santiago is interested in journeys. In the lab he studies the complex growth trajectories of axons—the thin, tube-like output structures of neurons, which carry information from one part of the brain to another. He wants to understand how axons trek through dense neural terrain to get to their target destinations and connect with the right partner cells, and identify the molecules that choreograph this growth process. But Santiago, a PhD student in the Program in Neuroscience at Harvard, also wants to understand the growth trajectories of people. In particular, he’s interested in the personal journeys that bring scientists into the lab—and what might be done to make sure there are roads into academic science for kids of diverse economic and cultural backgrounds.
As a child Santiago had many ambitions. He wanted to be second baseman for the New York Mets, as well as an astronaut—and not just any astronaut, but ‘the first man to walk on Mars.’ He also considered becoming a doctor or police officer. In high school Santiago generally performed well, but felt he graduated without identifying his true ‘passion’. When he enrolled at the City College of New York (CCNY), biomedical research certainly wasn’t at the top of his list of career options. He felt the need to study something more practical and profitable, like engineering.
Santiago attributes the fact he ended up years later in the neurobiology PhD program at Harvard, ardently studying fruit fly brains, to two exceptional educators and the support of RISE, a National Institutes of Health outreach program for undergraduates. He loves telling the story of how he became enamored with basic research and is eager to inspire others with this story.
A transformative teacher
Santiago’s education at CCNY was interrupted for a period of time, so that he could work many hours at Blockbuster to alleviate the financial burdens his family faced at the time. When he came back, he was feeling a bit lost. “I took classes here and there, testing the waters, trying to find something to grab onto, or something to grab onto me,” he explains. Then he signed up for a genetics course with biology professor Tadmiri Venkatesh and all of that changed. “I was completely enamored with the way he answered questions,” Santiago says. “He made himself available after class every day and was very patient… I was a huge fan of his.”
Ivan Santiago with Dr. Tadmiri Venkatesh, the CCNY professor who inspired him to study biology.
One day Santiago received a letter from Millicent Roth, director of the City College Academy for Professional Preparation, inviting him to engage in CCNY’s undergraduate research program. He was intrigued and made an appointment to meet with her. “At the time I hadn’t realized there were opportunities for undergraduates to do research,” he notes.
When Roth asked what labs interested Santiago, he mentioned how much he enjoyed Venkatesh’s course and decided to look into what the professor studied. It turned out Venkatesh’s lab was a neuroscience lab focused on glial cells—non-neuronal cells which fill the nervous system and largely outnumber neurons, but remain enigmatic—their contributions often over-shadowed by all the attention neurons receive. In particular, Venkatesh studies the role of glial cells in brain development and neurodegenerative diseases. This drew Santiago in, as he realized he’d always been curious about the brain and had often wished to understand more about brain conditions such as dementia and stroke, which affected close relatives.
The RISE program, designed to increase access of underrepresented minorities to biomedical research, sponsored Santiago to work in Venkatesh’s lab for three years. “That was definitely a life-changing experience for me,” Santiago says. “In his lab is where my scientific curiosity blossomed into a scientific passion.”
“To this day, I love being with people when they are looking into the confocal for the first time.”
There were two pivotal moments that shaped his decision to pursue a PhD and apply to Harvard. The first was when the graduate student he’d been working with for years finished up and Santiago was forced to start working more independently. He found the opportunity to start shaping his own research questions very exciting, challenging as it was.
The second was when he attended a conference at Cold Spring Harbor Laboratory. “That was really inspiring,” he says. “I was communicating with people who I had known only through their publications.”
Another memorable experience that fueled his desire to attend graduate school was the first time Santiago looked into a confocal microscope and saw fluorescent cells. Specifically, he was looking at glowing red glial cells and seeing firsthand evidence that perturbations of those cells could lead to neurodegeneration. “To this day,” he declares with enthusiasm, “I love being with people when they are looking into the confocal for the first time.”
Navigating neural landscapes
When he came to Harvard, Santiago remained interested in brain development and couldn’t draw himself away from fruit flies. “The genetic tools that are available in the fly are so extensive and precise,” he notes, as he begins extoling their virtues. “I can wake up one day and say, ‘You know what, I want to study this gene in this specific cell—throughout development.’ And I could likely do it with exquisite precision.”
Santiago works in the lab of Matthew Pecot, Assistant Professor of Neurobiology at Harvard Medical School. “Our lab is largely interested in how neurons are able to connect with their proper partners,” he says. “One of the most amazing aspects of the brain is that cells are able to connect with certain cells and ignore others. This is the basis for the development of proper neural circuitry—which is the cellular underpinning of the generation of behavior and brain function.”
Santiago goes on to explain that synapses, the points of communication between neurons—where axon terminals release chemical signals onto dendrites, the tree-like input structures of neurons—are often organized into distinct layers. These layers are found within ‘neuropil’, or neural terrain that is sparse in neuron cell bodies yet rich in axons, dendrites, and synapses.
“You can actually see these laminated patterns throughout these synaptic areas that are called neuropil,” he says. “And the questions we ask are centered on how neurons are able to infiltrate a neuropil and once they are there, position themselves within a specific region throughout that much larger space.”
“One of the most amazing aspects of the brain is that cells are able to connect with certain cells and ignore others.”
“The thought is that once a neuron gets to this very big space, it’s got all these potential partners to synapse with. But if you’re able to segregate that neuron into a specific region, then you limit the amount of potential partners that it interacts with,” he adds. “And that limits the potential errors that can occur during the process of synapse formation.”
Currently Santiago is examining the way an axon carrying motion information from the eye to the brain in fruit flies settles upon the right target region. He’s identified an interesting master gene regulator, or transcription factor, that appears to orchestrate multiple steps in the targeting process (which is complex, because the axon doesn’t just grow straight to its final destination, as one might guess). Now, he is trying to figure out the molecular strategy by which that transcription factor exerts its control over axons. One hypothesis is that the factor controls the expression of molecules in the cell membrane of the axon that interact with the extracellular space and other neurons.
A dream that ‘burns something inside’
Santiago says that coming to Harvard for graduate school has so far been the best decision of his life. He was the first member of Pecot’s lab and has been thrilled with the opportunities he has had to develop and drive his own research, as well as the support he’s received from Pecot, other lab members and the graduate program.
“When you come to Harvard, with its name, there’s always a preconceived notion for a place like this. That it’s like a castle on a hill with a steep incline, and you’ll have to claw your way up to be successful,” Santiago begins. “But at least within the Program in Neuroscience and the Department of Neurobiology, I can say from experience it is not like that. It is so warm.”
This is not to say that Santiago has faced no major difficulties in graduate school or can’t see areas for improvement in the PhD program he’s part of. In fact, it’s quite the opposite. Much of the praise he sings for the program stems from the support he’s found in dealing with challenges.
“One of the things I wasn’t expecting was how hard it was going to be as an under-represented minority,” Santiago says. “I knew that it would be difficult, but I didn’t know how difficult.”
“To be around your own kind is powerfully comforting, something that I did not appreciate until graduate school.”
Recently named a Howard Hughes Medical Institute Gilliam Fellow in honor of his past achievements and future promise in research, as well as his commitment to increasing diversity in science, Santiago shares an excerpt from the application essay where he explains this difficulty: “Growing up in the South Bronx, and attending schools in New York City, I was always surrounded by minorities, which formed a sense of security. To be around your own kind is powerfully comforting, something that I did not appreciate until graduate school. I experienced a failed sense of belonging and a heightened sense of insecurity.”
He goes on to share that there was a period where he wondered if he’d been offered admission to fill some quota. He describes feeling a ‘self-imposed pressure’ that if he failed, it would affect opportunities for others of his racial or ethnic background. It was only when he reached out to other students across the university who were also under-represented minorities that he realized this was a common experience.
In 2015, consulting with Rosalind Segal, director of the neuroscience PhD program at Harvard, as well as Benyam Kinde—another Gilliam Fellow student who just this year graduated from the program, Santiago worked to launch a group called “USN” or Underrepresented Students in Neuroscience. The group is still in its early days, but has made significant strides—most notably in the recruitment of underrepresented minorities to the graduate program and in providing support for students and post-doctoral fellows who are at Harvard. This year, Santiago says, the graduate program was able to recruit as many under-represented minorities as it has in the previous three years combined, and to establish a new peer mentoring program.
“The USN program has improved our ability to recruit and support talented students from diverse backgrounds, and has greatly enhanced the Program in Neuroscience overall,” Segal states.
Santiago has also volunteered for HPREP and SHURP—summer programs at Harvard that serve high school and undergraduate students from under-represented or under-served populations seeking to explore science careers.
“Funding students—not so they can go out and buy an iPad, but so they can focus on a textbook, or spend five hours a day looking into a microscope—rather than stocking shelves at a Walmart—is crucial.”
Asked to explain a bit more about the disparities that such programs help to address, Santiago says, “My story is the perfect example.” Because his family had fallen on hard times economically, he had to work many hours outside of college before he learned about the RISE program. If it weren’t for the financial support that program provided, he might not have had the time to work in the lab in addition to taking classes—and thus would have been a far less competitive candidate when applying to graduate school. Or might not have even realized he wanted to go to graduate school.
“People from where I come from are not only under-represented minorities, but also economically disadvantaged,” he explains. “Funding students—not so they can go out and buy an iPad, but so they can focus on a textbook, or spend five hours a day looking into a microscope—rather than stocking shelves at Walmart—is crucial.”
Santiago’s long term aspiration—a dream that ‘burns something inside’—is to take what he learns at Harvard and ultimately go back to start his own lab at CCNY, so he can increase opportunities for students from backgrounds similar to his own.
In addition to his desire to increase diversity in science and introduce under-privileged students to the joys of research, Santiago dreams of becoming a professor for the simple reason that he loves to teach. Thinking about creative new ways to explain complex concepts such as action potentials to newcomers in neuroscience enthralls him. In fact, as an undergraduate Santiago taught a biology course where he designed and delivered his own lectures—a unique opportunity for an undergraduate, or even graduate, student, who typically would serve mainly as a teaching assistant.
So what’s the secret to being a great teacher?
Santiago modestly says he might not be qualified to answer that question yet. “But I think that you have to be able to listen well. For what is being said and not being said,” he observes. “You have to really absorb and appreciate the human aspect of what you’re doing. Because there is so much that goes on outside of science in people’s personal lives.”