Physicians use sophisticated tools, such as electroencephalograms, or EEGs, to diagnose and monitor brain disorders, but they see only the electrical impulses, which is a bit like hearing two people talking but not understanding what they are saying, says Nako Nakatsuka, Ph.D., a chemist at ETH Zürich in Switzerland. “It’s like a very muffled conversation.”

Scientists have struggled to identify those complex chemical interactions at the time they occur. Often, that requires extracting liquid from the brain and putting it through tedious purification techniques in the lab, a process that can take days.

“I wanted to be able to insert a sensor close to where these interactions happen and monitor this chemical flux in real time,” says Nakatsuka, a 2012 Fordham College at Rose Hill graduate who has spent the past several years developing a chemical biosensor to do just that. The technology she created consists of a glass pipette tapering to just 10 nanometers at its tip, able to get in close proximity to synapses and monitor chemicals at the source. “We’re using nanotechnology to approach the dimensions at which the chemistry happens,” Nakatsuka says.

The invention earned her a spot this year on MIT Technology Review’s list of “35 Innovators Under 35” (out of over 500 nominations). More importantly, it could revolutionize the study of diseases such as Alzheimer’s and Parkinson’s by allowing neuroscientists to truly understand, for the first time, chemical interactions inside the brain as they occur.

Into the World of Bionanotechnology

Nakatsuka spent her formative years attending an all-girls school in Japan, where she was just as interested in art and athletics as she was in science.

“I was able to grow into myself and be confident in the things I liked and pursued without issues such as body image or imposter syndrome,” she says. “No one ever told me, ‘You can’t do that because you are a girl.’” Inspired by hands-on chemistry experiments in high school, she decided to pursue the subject at Fordham, where she also ran competitively on the cross country and track and field team.

An unexpected connection between sports and science led to her interest in nanotechnology. She was taking a course in organic chemistry, and professor Ipsita Banerjee, Ph.D., was her lab instructor. “I was ranting to her about how I had no idea how this stuff was applicable to real life,” remembers Nakatsuka, who at the time had torn a ligament and tendon in her ankle while running, and was on crutches and wearing a walking boot. Banerjee told her about her research in tissue engineering. “She said, ‘Imagine if you could heal yourself by using biocomposites you created in a lab that could mimic the tissue in your body, rather than getting surgery and being out of commission for a year.’”

Nakatsuka was fascinated by the idea. She joined Banerjee’s lab the following fall and plunged into the world of bionanotechnology, a highly interdisciplinary field focused on developing biomolecular composites for biomedical applications in tissue engineering, biosensors, and drug delivery. “She was my scientific savior at a time when I was pretty lost and didn’t know how to focus my energy,” Nakatsuka says. “She really put in a lot of time and effort in developing my potential as a scientist.”

At the time, Fordham lacked much of the equipment necessary for Banerjee’s nanotechnology research, so she would drive her students to Queens College, part of the City University of New York, where a colleague allowed them to use the equipment in his lab. Initially, Banerjee was worried that Nakatsuka’s sports schedule would keep her from the necessary work. Instead, she found her to be an incredibly dedicated researcher. “It didn’t matter if she had exams, or had a meet somewhere, I could rely on her,” Banerjee says. The two developed a tight bond, with the professor sometimes dropping Nakatsuka back at her dorm at 3 a.m. after a night of experiments in the lab and animated conversations about science over breakfast at an all-night diner.

“Since we don’t have a graduate program, I expect graduate-level work from my research students,” Banerjee says. Nakatsuka rose to the challenge, becoming lead author on a review paper on tissue engineering, and co-authoring seven other peer-reviewed papers with Banerjee during her time at Fordham.

Catching the Brain’s Chemical Signals

While presenting one of their papers at an American Chemical Society national meeting in San Diego, Banerjee and Nakatsuka met with Paul Weiss, Ph.D., a UCLA professor and nanotechnology pioneer whose research group combines science, engineering, and medicine. The ability to make a practical difference appealed to Nakatsuka, who joined Weiss’ group as a doctoral candidate after graduating from Fordham.

“It fascinated me to think about using chemistry and biology to do something I was passionate about, and contribute to society,” she says. While there, she began working with aptamers, short single strands of DNA that are specifically designed to attach themselves onto a chemical target.

Nakatsuka was intrigued by the ability these aptamers have to change their shape when latching onto their prey. “It is like when the fingers of a baseball glove come down to capture a ball,” she explains. “They structure switch.”

Nakatsuka began using that property to create a sensor that could detect the presence of a specific chemical in the body. Existing biosensors have struggled to differentiate similar molecules from one another accurately, especially when the desired chemical is in short supply.

“It’s like trying to find and capture one fish in a sea of similar-looking fish that exist in much higher amounts,” Nakatsuka says. Collaborating with nanoscientists and engineers, she created an ingenious probe with a tiny pore at one end that was covered in aptamers designed to capture a specific neurochemical such as serotonin, along with several electrodes. When serotonin was present, the aptamers would switch their structure to make the nanoscale opening more porous, and alter the electrical flow that could be measured by scientists in real time. By calibrating the sensor in advance, they could even tell how much serotonin was present in a given sample.

Toward a Better Understanding of Brain and Body Health

After designing the sensor and earning a Ph.D. at UCLA, Nakatsuka moved to ETH Zürich, a scientific institute with a specialized Laboratory of Biosensors and Bioelectronics, for a postdoctoral fellowship in 2018. She’s now a senior scientist there, working with a team of neuroscientists to train the sensors to detect neurochemicals that could provide new insights into Alzheimer’s and Parkinson’s, for example, by quantifying neurochemicals in the brain and blood associated with those diseases.

“What’s exciting to me is that there are neuroscience groups that have been focused on one question for a long time—for example, understanding how dopamine is regulated in brain development, or how serotonin is regulated in anxiety and depression,” Nakatsuka says. By distributing her kits to these scientists, she says, she can provide new tools to generate data and answer some of those questions in a much quicker and easier way.

While Nakatsuka’s sensors are currently being used only in the laboratory, she hopes that eventually they could be used in the body, inserted like an acupuncture needle to monitor brain chemistry in patients. They could have applications beyond neuroscience, as well, providing an ability to detect chemicals anywhere in the body—for example, monitoring iron in anemic patients or stress biomarkers for people with anxiety disorders. She envisions people wearing a Band-Aid-like device with the nanopores integrated inside that could withdraw small amounts of blood with a tiny needle to provide ongoing monitoring. “That’s more of an engineering challenge,” she says. “But it’s really not crazy to imagine implementing it in a way that is practical and applicable for daily use.”

From such tiny beginnings, Nakatsuka’s nanosensors have big potential, giving scientists new ways to understand and monitor diseases throughout the body. “Now I often hear, ‘Are you going to commercialize this? When are you going to go on the market?’” she says. “To be honest, I never thought about it, but now it’s something I want to start looking into to see how I might make a larger impact.”

—Michael Blanding is a journalist and the author of three books, including North by Shakespeare: A Rogue Scholar’s Quest for the Truth Behind the Bard’s Work (Hachette, 2021).

Describing all this nighttime cleanup and repair work, Dr. Daniel Barone makes one thing clear: There’s a lot we still don’t know about slumber and the disorders that impede it.

But he makes other things clear too: Better sleep is attainable for those who seek it. And, in our sleep-deprived society, more people need to do that, he says, citing dangers ranging from disease to traffic accidents to everyday fogginess.

“I have a lot of patients come to me and say, ‘You know what, I’m just not as sharp as I used to be,’” he tells an audience at Webster Library on Manhattan’s Upper East Side during a presentation in July. “‘I’m not as quick as I used to be. I go into a room, I can’t remember why I’m there,’ that kind of stuff.

“There’s other reasons for that, possibly, but one of them is sleep,” says Barone, assistant professor of neurology at Weill Cornell Medicine and associate medical director of the Center for Sleep Medicine at New York-Presbyterian/Weill Cornell Medical Center.

Barone, a 2001 graduate of Fordham College at Rose Hill, serves as an increasingly public expert on sleep, appearing in media outlets and giving talks around New York. He’s finding receptive audiences and many opportunities to speak, given the growing concern about sleep deprivation, labeled a “public health epidemic” by the U.S. Centers for Disease Control and Prevention because of its links to depression, anxiety, hypertension, obesity, and cancer.

If sleep is essential, however, it’s also frustratingly hard to attain for many, one reason Barone recently authored Let’s Talk About Sleep: A Guide to Understanding and Improving Your Slumber (Rowman & Littlefield, 2018).

Written with Lawrence A. Armour, it tells the stories of patients who found their way to better slumber through considerable patience, persistence, and trial and error. Despite all the recent scientific and technological advances in the field of sleep, there are no quick fixes or standard solutions. As Barone describes it, the quest for better sleep involves not only science, medicine, and proven practices, but also a certain amount of faith.

Discovering Sleep Science

Barone grew up on Long Island, in Franklin Square, studied biology on a premed track at Fordham, and earned his medical degree from New York Medical College in Valhalla, New York. He first learned about sleep medicine when he was in residency at Saint Vincent’s Catholic Medical Center in New York City. A visiting lecturer spoke about it, and Barone was fascinated.

He went on to complete a one-year fellowship in sleep medicine at Stony Brook University and earned board certifications in neurology and sleep medicine from the American Board of Psychiatry and Neurology.

In a way, sleep medicine is still a “great frontier” because of all its unknowns, he says. Some aspects are well established: When light dims, nerve cells in the eye signal the brain’s pineal gland to release melatonin, which readies the body for sleep. While we slumber, long-term memories are solidified as the brain pares back some nerve connections and strengthens others, Barone says. And because it is a powerful antioxidant, melatonin also cleans up free radicals, metabolic byproducts that could damage cells and pave the way for heart disease or cancer.

Other functions of sleep have only recently come to light. In 2012, researchers at the University of Rochester Medical Center discovered the glymphatic system, a kind of “shadow plumbing system” in the brain, according to a university statement. It fires up only during slumber, flushing out toxins that build up during the day, including those linked to Alzheimer’s and Parkinson’s diseases. Some brain cells actually shrink to accommodate this outflow, Barone says.

But many aspects of slumber are still poorly understood, like the tipping point between our waking and sleeping states, as shown by the fact that “we never remember the exact moment at which sleep onset occurs,” Barone writes in the book.

Sleep disorders offer up plenty of unknowns as well. Barone’s research focus is REM behavior disorder, in which people act out their dreams during the rapid-eye-movement stage of sleep. Other scientists are studying restless legs syndrome, one condition that impedes the slumber of Barone’s patients. “We know so much about the brain, but there’s still a lot we don’t understand about restless legs syndrome,” he says.

A Concern for All Ages

Some sleep disruptors are better understood, like blue light from computer screens, which keeps nerve cells in the eye from triggering the release of melatonin. One of the most common disorders is sleep apnea, in which the tongue repeatedly falls back to block the airway, interrupting sleep and causing daytime drowsiness. It afflicts as many as one-quarter of middle-aged men and 9 percent of women, according to Barone, although its severity varies.

His patients have often been sleep deprived and exhausted for years. They may struggle to fall asleep, wake up too early, or wake up tired after a full night’s slumber. Some only learn about their disorders after spending a night in the Weill Cornell sleep clinic, hooked up to monitoring equipment.

Let’s Talk About Sleep includes a variety of stories from patients (identified only by first names) who volunteered to be interviewed for the book. They tend to be middle-aged or older, as sleep tends to degrade with age because of weight gain, hormonal changes, prostate issues, or other things, he says.

But young people are hardly immune to sleep troubles. As Barone describes in his book, one patient’s sleep disorder—narcolepsy—emerged in high school, causing her to fall asleep in class. And sleep needs to be a big priority for college students, no matter how overstuffed their schedules are, Barone says, noting that sleep loss is linked to anxiety and depression, and can also get in the way of one’s studies.

Barone has some experience with this. After studying all night for tests as an undergraduate at Fordham, he found that he didn’t remember much of anything unless he found time to sleep. In fact, a quick nap was enough. “I remember thinking, ‘That’s pretty amazing—just a little bit of sleep actually helps you to retain the information.’ Without it, it was almost impossible.”

Treating Sleep Loss

Treatments vary from patient to patient. Medication is just one, often short-term, option. Behavior changes, like avoiding electronic screens before bed, are also important. For insomnia, one of Barone’s preferred techniques is mindfulness meditation, which activates the relaxing parasympathetic nervous system, improving not only sleep but also one’s general mindset, he says.

Technology also plays a role. Sleep apnea patients, for instance, may use a continuous positive airway pressure, or CPAP, mask that feeds pressurized air into their airways overnight, allowing them to sleep uninterrupted. Their other options include a dental device that pulls the jaw forward, keeping the tongue away from the back of the throat, or positioning devices to ensure they sleep on their side. One new option is a device implanted in the chest that electrically stimulates the hypoglossal nerve to keep the tongue from collapsing backward.

Whatever the sleep issue, the patient’s attitude is key, Barone says. Another patient mentioned in Let’s Talk About Sleep, a 61-year-old married mother of two, was waking up at midnight or 1 a.m. and tossing and turning for the rest of the night. This problem had persisted for 15 or 20 years. Then she heard an expert speak about the ill effects of sleep loss. The presentation hit home; she realized that she was in fact noticing some of the effects, like rising blood pressure, so she changed her “tough it out” attitude and sought help.

In consultation with Barone, she devised a regimen including progressive muscle relaxation, regular bedtimes, and the use of an alarm clock. Over time, her sleep improved. “It has made an incredible difference in my life,” she says in the book.

One of the most important changes she made was psychological. She developed what she called “an overall appreciation for the importance of sleep.” This appreciation doesn’t always take hold easily in the U.S., where the ability to do without sleep is viewed “almost like a badge of honor,” Barone says. “I’ve been guilty of that myself.”

Slighting the Sandman

Adults generally need seven to nine hours of sleep per night on average, according to the National Sleep Foundation. But, as stated in the book, more than a third of Americans are regularly getting inadequate shuteye. And some 50 to 70 million Americans suffer from chronic sleep disorders and periodic sleep problems, according to the National Institutes of Health.

People can be blind to the impact of sleep loss. Barone noted that one 2003 study by researchers at Harvard and the University of Pennsylvania found that people limited to six hours of sleep or less for several nights were just as impaired in a simple attention test as those who had missed as much as two whole nights of sleep.

All the same, the participants thought their bodies and minds were adjusting to the sleep loss, and that they were “doing OK” on the attention test. “In reality, they were not doing OK,” Barone says. “They were making a lot of mistakes,” and “this is just a small scale. You can imagine what’s happening when sleep deprivation is much more chronic,” he adds, naming motorists’ impaired reaction times in particular.

Such concerns are one reason why the U.S. Centers for Disease Control and Prevention has described sleep deprivation as a public health epidemic, and why Barone has accepted so many invitations to speak publicly. He hopes that it will eventually be recognized that “lack of quality sleep for a long period of time is as bad for us as smoking,” he says.

Dreaming of Better Sleep

One of sleep’s greatest mysteries is dreaming, a particular interest of Barone’s. He and other researchers are in the midst of a privately funded three-year study of REM behavior disorder, caused by a failure of the sleep paralysis that usually keeps people from acting out their dreams. Someone dreaming about being in a fight, for instance, might thrash about in bed, Barone says. While this kind of thing is alarming, the real concern—and the focus of the study—is the link between this disorder and Parkinson’s disease, he says.

The possible benefits of dreams are the biggest question mark of all. “There must be a good reason” for them, given the amount of brainpower they require, Barone writes; the sleeping brain not only generates the content of dreams but also the slumbering mind’s experience of them, a level of activity that indicates that dreaming “is not some random thing,” he writes.

Theories abound: Dreaming may prepare us for the stresses and threats of waking life by providing a kind of dry run during sleep. They may provide a “theater of the mind” in which we work through problems, or allow us to test out emotional reactions to various situations. “There’s probably 10 different theories as to why we dream. Nobody knows for sure,” Barone says. “The brain is beyond complex,” with 100 billion neurons interacting in uncounted trillions of ways.

In Let’s Talk About Sleep, he conveys respect for sleep and the need to give it its due. Rather than serve as a medical text, the book is meant to stimulate interest in sleep, Barone writes; he urges readers to talk to a doctor about their particular sleep troubles and medical concerns. In his July presentation, he offered some tips for getting better sleep generally, like exercising and setting regular bedtimes. And he made it clear that being patient and putting one’s expectations on the shelf were also important. “None of these things are going to change your sleep overnight—pun intended,” he said.

His patients may work for weeks, months, or longer, trying different approaches and laying the groundwork for better sleep, which he describes as something to be encouraged, coaxed, cajoled. Or won over, perhaps.

“I always say, sleep is kind of like love,” Barone says. You can do all the right things and put yourself in a position to make it happen, he says, but ultimately it follows its own timetable. “I always tell patients, ‘Let me worry about your sleep. You just concentrate on doing the right things, and eventually sleep will happen.’”

See Related: Seven Tips for Better Sleep

Months into her battle with Alzheimer’s, Jessica Morales’ mom developed aspiration pneumonia—the most common cause of death for Alzheimer’s patients. Breathing problems and infections led to frequent and frustrating trips to the emergency room. Morales knew her mother was dying. But she also knew she needed more extensive care than could be provided at home. So she brought her to Calvary Hospital in the Bronx, where staff treated her physical symptoms and so much more.

“I knew I needed the support to get through this time with her,” said Morales, FCRH ’97, an actress who grew up on the Lower East Side of Manhattan. ““The care there was so different from the beginning.” Hospital staff turned her mother in her bed every two hours, she said, brushed her hair the way she liked, and played her favorite Mexican music to soothe her. “It was an individualized approach.”

“Every time we have a meeting here, everybody’s hugging,” said Michael J. Brescia, MD, FCRH ’54, Calvary’s executive medical director. It’s a side effect, he said, of the culture of the facility, where alleviating emotional and spiritual suffering is as crucial as treating the physical symptoms of disease. “You have to touch your patients. You have to hold their hands. And it’s got to mean something to you.”

Fordham and Calvary have enjoyed a close relationship for years, forged in part by Brescia’s love for his alma mater. “Fordham gave me the gift of faith,” said Brescia, who says a silent prayer each time he enters a patient’s room. That personal connection led to a professional partnership. Fordham faculty have conducted research at Calvary, and Calvary medical staff have lectured in Fordham programs. An October 20 symposium at the University highlighted that research, fostering a discussion on the complex issues surrounding palliative care.

Mary Beth Morrissey, PhD, FCRH ’79, LAW ’82, GSS ’11, a healthcare attorney and researcher, and the director of Fordham’s Healthcare Management Certificate Program in Public Health, Palliative Care, and Long-Term Care, organized the conference.

“The relationship with Calvary is a very meaningful one for Fordham,” she said, particularly when it comes to research. “Our faculty is working across the whole spectrum of palliative care.” In one study, Fordham psychologist Barry Rosenfeld, PhD, and Fordham psychology graduate students explored meaning-centered talk therapy with Calvary patients as a way to provide a sense of peace at the end of life. “We’re trying to understand that palliative care is both medical and social,” Morrissey said.

Insurance companies have been slow to fund palliative care, and so Morrissey and her colleagues aim to put it in the larger context of healthcare reform and value. “This is really about changing a cultural paradigm,” she said. “I think the problem is, in our Western culture, we have been very reluctant as a society to engage in any discussions about limits on care or how we’re going to allocate resources.”

Fixing a Broken System

Presenting the keynote at the October 20 conference was Philip Pizzo, MD, FCRH ’66, pediatric oncologist and former dean of the Stanford School of Medicine. A nationally respected policy advocate, Pizzo has helped lead major studies on palliative care and end-of-life care for the Institute of Medicine: the groundbreaking Relieving Pain in America, published in 2011, and last year’s Dying in America: Improving Quality and Honoring Individual Preferences Near the End of Life.

“It’s not whether to choose more or less care, but whether to honor individual preferences,” said Pizzo, a microbiology and immunology professor at Stanford and founding director of the university’s Distinguished Careers Institute. And pain, he points out, is not just an end-of-life issue. An estimated 100 million people in America suffer from chronic pain. A few years ago, he became one of them. “It became very personal,” he said of the chronic neuropathic pain he experienced after an injury. “Suddenly I was completely incapacitated, so I absolutely appreciated how it literally saps the energy and the sense of purpose from anyone.”

At Calvary, Brescia and his staff view depression and psychological pain as one of several types of suffering to focus on when caring for patients. Patients also struggle with spiritual suffering, he said, asking themselves, “Is there a supreme God that loves me and knows what I’m going through?” And Calvary staff are equally cognizant of familial suffering. Morales, who slept on a cot in her mother’s room during her stay at Calvary, received a massage through the Family Care Center, which she called “a little haven.” And when her mom died, a Calvary chaplain was there at Morales’ side.

When it comes to physical suffering, hospital staff fight aggressively, Brescia said. Calvary physicians have worked to find alternate methods of delivering opioids for pain relief, and they’ve perfected techniques like using a gastrostomy tube to alleviate nausea common in end-stage cancer patients.

Cost Versus Value

That kind of comprehensive care is not without its costs. Calvary, a nonprofit, loses millions of dollars a year, much of it made up in fundraising. But the world-renowned physician was never in this work for the money.

Before he got involved in palliative care, Brescia achieved fame in the mid-1960s for the Brescia-Cimino fistula, a surgically created connection between veins and arteries used in hemodialysis patients. People came to the Bronx from all over to be treated for chronic kidney disease, he said, and Calvary was beginning to collect full compensation for dialysis so they could build a new facility.

“But I went to tell my father, a little Italian immigrant,” Brescia said. He explained the invention and said that centers would open around the world in a year’s time, and he’d stand to make quite a bit of money. The older man said, “A year? Why a year?” When Brescia explained that it would take time to set up the lucrative contracts, his father asked, “How many die in a year?” Brescia told him 50,000, and his father’s face dropped. “‘Give it away,’” he told his son in Italian. When Brescia protested, his father said, “‘When you shave in the morning, the faces of the children will appear in the mirror, [children]who should be with their parents. They will not be because my son, who I should be so proud of, has to have five cars, five boats, five houses.” Brescia knew his father was right. “I left his house and [we]published [the research].”

Clinicians began using the procedure and contacting Brescia for his expertise. “Doors just opened,” said Brescia, who is considered a pioneer in modern palliative care. “They wanted to hear about all the renal work. The price of that was that they had to hear about the palliative work,” which he was now doing at Calvary. He said he and his colleagues were able to get many federal laws passed “that enabled us to survive and prosper.”

Collaborating on Care

But getting insurance companies to cover the cost of palliative care is still a challenge, despite the empirical evidence that it lowers hospital readmission rates, said Falguni Sen, PhD. Sen directs the Global Healthcare Innovation Management Center at Fordham, which presented the October 20 panel discussion in conjunction with the Fordham Science Council.

“Palliative care, in my opinion, has been the first group that has really tried to look at healthcare in an integrated way,” he said, noting that the Affordable Care Act has given providers some options through which they can include palliative care. He cited new accountable care organizations that accept a total fee for the care and well-being of Medicare patients rather than a traditional fee-for-service arrangement.

Sen said his center, part of the Gabelli School of Business, aims to build on Fordham’s collaborations with Calvary Hospital to explore programs based on these new provisions. He hopes to expand the University’s certificate program in palliative care—which includes Calvary medical staff as instructors—to offer “more skill-based” programs. The University’s Graduate School of Social Service also offers an increasingly popular palliative care program, which has MSW students completing fieldwork at Calvary. And Sen anticipates Fordham faculty from several disciplines wanting to make a difference in the way care is delivered.

“We’ve got to move out of the purely medical care model on palliative care. It’s not just a question of managing pain through medication,” he said. “Pain is something that is so complicated … and it requires care and consideration on so many levels.”

Listen to Dr. Pizzo discuss palliative care and his work at the Distinguished Careers Institute on WFUV’s Fordham Conversations.