In Depth

Parkinson’s disease is a progressive disease of the nervous system that slowly robs people of their ability to move and think. Current treatments for Parkinson’s address only the symptoms of the disease, which include stiffness, slowness and mood disorders, but do nothing to halt the disease’s progression. With over 30 years of experience studying neurodegenerative diseases, Ted and Valina Dawson are paving the way for new treatments for this harrowing illness.

Once you’ve won a Nobel Prize, people are apt to refer to you as “Nobel laureate So-and-So” — as if the prize redefines your identity. And maybe it does for some, but for Hamilton “Ham” Smith, the Nobel Prize he won at age 47 didn’t change his interactions with people, and his prize-winning discovery involving one of the first molecular “scissors” was just the first of many landscape-altering discoveries. 

Using CRISPR-Cas9, a revolutionary gene-editing technique, Geraldine Seydoux can delete, replace, or reprogram a nematode gene at will—and then step back and observe the result. 

With huge troves of genomic and other types of research data, the so-called “under-the-desk” computer server is vastly underpowered to handle such large data sets. Johns Hopkins Medicinefaculty are now working with staff members in information technology to host research data on Microsoft- and Amazon-based cloud computing systems. 

Believed to be the first-of-its-kind training, the Johns Hopkins-MedImmune Scholars Program provides students with an opportunity to experience firsthand what is like to work for the pharmaceutical industry. After completing thee program, students can opt to a one-year internship at MedImmune  and gain skills in science writing, project management and clinical operations.

Meet Siobhán Cooke, assistant professor of functional anatomy and evolution. A spelunking paleontologist in the caves of the Caribbean, she is out to preserve the planet by sharing her understanding of historical extinctions, one fossil at a time. Similar to her pop culture counterpart Indiana Jones, Cooke teaches by day and devotes the rest of her time to paleontological research.

Core facilities play a fundamental role in supporting cutting-edge research by providing resources ranging from genome sequencing tools to biostatistics services. iLabs, a web-based resource, connects core facilities throughout Johns Hopkins, and the Core Coins program provides a new funding mechanism that promotes access to core facilities and innovative research.

One in three older adults will experience some form of dementia, so why are families not talking about it? Constantine Lyketsos and Paul Worley share the developments in treatment and advancements toward a cure to fight the silence.

After losing his grandpa to tuberculosis in Nepal, Gyanu Lamichhane works to eradicate one of the world’s top infectious killers by trying to understand how to exploit TB bacteria weaknesses. “All I want to do is kill TB. It’s a personal thing for me.” 

With its unique pedagogical approach, the Center for Bioengineering, Innovation and Design (CBID) master’s provides students with a 360 degree view of the biomedical device design process. By exposing students to every element of the design process in both high- and low-resource settings, CBID teaches students to be efficient and effective innovators.

The FDA approval of a drug targeting tumors based on genetics rather than type marked a milestone in precision medicine. Research at Johns Hopkins and elsewhere suggests the drug can help 1 in 25 advanced cancer patients who would otherwise have little hope of treatment.

Published in 1966, the Mendelian Inheritance in Man (MIM) catalog consisted of 1,487 descriptions of human genes, genetic disorders and traits compiled by Victor McKusick. Fifty years later, and now online, OMIM consists of more than 24,000 entries and  is accessed thousands of times every day by clinicians, researchers and others around the world.

By merging the best of immunology and the best of engineering researches created a new field – immunoengineering. From enhancing tissue regeneration to preventing the body’s rejection of medical implants to boosting the immune system this brand new field brings new possibilities for improving cancer treatments.

Back in 2006, an animated discussion over coffee about the possibility of synthesizing the entire yeast genome led two researchers to get to work. Now, just over a decade later, they and collaborators around the globe have succeeded in designing an entire synthetic yeast genome — and have already built six of its chromosomes.

Although cochlear implants help hearing impaired people to listen, they are not very good at distinguishing pitch or picking out voices in noisy environments. By studying marmosets, Xiaoqin Wang and his team aim understand how the brain processes complex sounds in hopes to improve cochlear implants

Language, music, art, planning, problem-solving, making tools. No other animal has all of these aptitudes. All rely on a single organ: the brain. But the brain is the most poorly understood organ of the human body. Seeking to change that is an interdisciplinary group of Johns Hopkins scientists, members of the Kavli Neuroscience Discovery Institute. Together, they are harnessing the brain’s problem-solving abilities to unlock the mysteries of neuroscience.

Evolutionary biologists in the Center for Functional Anatomy and Evolution put their own spin on anatomy classes. Lectures now include comparisons of human anatomy to other animals, giving students a deeper understanding of the science of the body. 

Could a green mosquito save lives? Read about the quest to engineer a malaria mosquito whose smell-detecting neurons glow – and its implications for the fight against the disease.

September 2016—Instead of needling mammalian brains to understand their workings at the cellular level, biomedical engineers Reza Shadmehr and Vikram Chib blend the fields of robotics, mathematics and economics to coax the human brain into letting us in on a few of its secrets.

Over a thousand students, whose interests span from biochemistry to mental health, apply to participate in the Johns Hopkins Summer Internship Program each year. Once accepted, they are paired with a Johns Hopkins researcher who guides them through what is, for many students, their first in-depth research experience. This opportunity helps students prepare for careers in medical research and healthcare. 

Most of us have the luxury of seeing mosquitoes as merely annoying. But mosquitoes are by far the most deadly animals in the world because of the illnesses they sometimes carry. This summer, scientists from Johns Hopkins and around the world are working from many angles to overcome the Zika virus threat.

When a person dies of unknown causes, the medical examiner does an autopsy. For animals, that service is provided by a veterinary pathologist. Those at Johns Hopkins partner with the Maryland Zoo and the National Aquarium, plus biomedical researchers and local vets, to provide insights into the best care for animals of all shapes and sizes.

Sex differences affecting the overall health of men and women have been recognized for years, but researchers have only recently begun to elucidate the underlying hormonal and genetic factors at play. Their findings have implications for diagnosis, public health messages and treatment of a wide variety of maladies.  

Andy Feinberg hopes to learn something about how long-term residence in space affects the human body by comparing biological samples from astronaut Scott Kelly — who recently returned from a year aboard the International Space Station — with those of his Earth-bound twin, Mark.

Three school of medicine graduate students volunteered as “Genome Geeks” at the National Museum of Natural History. In the words of one student, “I wanted to show [visitors] that science is accessible and scientists are approachable.” It turns out that the benefits of that engagement flow both ways.

Biomedical engineer Justin Hanes innovates new ways of getting drugs past mucus barriers to treat mucus-protected areas like the eyes. Then he uses his business sense to get solutions out of the lab and into patients’ hands where they can make a difference.

Researchers and clinicians are working together to learn everything they can about the mutations that cause cystic fibrosis and their effects on patients.

Youyou Tu's Nobel prize has brought renewed attention to the dynamic relationship between Chinese and Western medicine. At Johns Hopkins, two faculty members from very different fields are exploring that relationship in their own ways: one by studying its history, the other by figuring out how one traditional Chinese medicine works.

Researchers at Johns Hopkins are now in the early stages of figuring out how the composition of the gut changes in different diseases, how the body’s immune system interacts with these tiny hitchhikers and particularly how that relationship may function in disease. 

Geneticist Ada Hamosh got a call from the neonatal intensive care unit to see a baby with a strange combination of symptoms: He had a brain bleed and almost no nose, two seemingly unrelated traits Hamosh had never seen together before. She knew that she didn't have much time before the hemorrhaging damaged the baby's brain irreparably. She did a quick search in a database known as Online Mendelian Inheritance in Man. Based on similar reported cases, she learned that what the baby needed was an immediate infusion of vitamin K.

The contents of your trash bin reveal a lot about you: what you ate recently, whether your kids are in diapers and how much you recycle. Cells throw things out too. Little sacs of cellular material constantly bud off of their outer membranes, carrying cellular garbage with them. Though it's a common phenomenon, we don't know exactly what the purpose of these sacs is, but several researchers at Johns Hopkins are now scrutinizing this cellular trash to find out.  

The protests and unrest following Freddie Gray’s death while in police custody this spring brought renewed attention to inequality in Baltimore and the lack of upward mobility in many of the city’s neighborhoods. But how best to attract high-quality jobs to the city and ensure that local residents are qualified for them, are questions that defy quick solutions. For years, the faculty and staff members at Johns Hopkins have been dedicated to feeding the curiosity of Baltimore’s youth and providing them with valuable experiences and mentorship.

Science isn’t complete until it’s communicated. But sometimes, words alone won’t do a subject justice, especially when a discovery demands to be shared with the whole world. It is then that art and science become perfect partners. At Johns Hopkins, science and art formalized their relationship more than a century ago with the founding of the Department of Art as Applied to Medicine.

For 30 years, neuroscientist Rick Huganir has been studying what happens as the brain learns new information. Until recently, his research entailed teaching mice new tricks and then euthanizing them before probing their brain tissue under a microscope. But in the past few years, Huganir' has been using a new technique that lets him watch the real-time molecular changes that occur as a mouse learns. All he has to do is look through a window into its brain.

CT and MRI scanners are workhorses of modern medical imaging, yet their large size, expense and limitations in imaging dynamic structures like the heart limit their capabilities. By pushing the bounds of those technologies to make them more versatile, researchers at the Johns Hopkins University School of Medicine are changing how medicine is practiced.

Though driving knowledge forward at an unprecedented speed, the age of "big data" has created a divide between the bioinformatics “haves” and “have-nots,” crowding out those with big ideas but providing little access to expensive equipment and infrastructure. With the opening of a new center, Johns Hopkins aims to democratize the big data revolution, putting top-of-the-line computing power within reach of every researcher.

Dara Kraitchman started the Center for Image-Guided Animal Therapy partly out of a desire to extend the benefits of medical advances to furry patients. In doing so, Kraitchman and her colleagues aim to advance care not only for pets, but ultimately for people.

Earning a biomedical Ph.D. has been chiefly associated with an academic research career, but an increasing number of biomedical graduate students are choosing other career paths. A new program at the Johns Hopkins University School of Medicine is helping students identify where they want to go and how they can get there.

Through a combination of targeted physical and molecular testing, a clinic at Johns Hopkins, called the Epigenetics and Chromatin Clinic, aims to provide parents of children with rare epigenetic diseases with a fast and accurate diagnosis. The goal is to move epigenetics research out of the realm of basic science and into medicine.

Yeast—the single-celled organism that makes life’s most delicious beers and breads—doesn’t really “grow old” like humans do, but it is helping us unlock the secrets of aging. It may even provide the key to stopping the premature aging of children with the ultrarare disease Hutchinson-Gilford progeria syndrome.

For years, Anthony Cammarato has been studying fly hearts, which he suspects can provide insight into heart disease in humans. 

Albert Chi is on the forefront of designing high-tech artificial limbs, or prostheses. He was troubled to have little to offer parents of children born with limb deficiencies whose insurance companies declined to pay $50,000 for a prosthesis that would only fit the growing kids for a few months. Thus began his exploration of 3-D printing, a technology that is adding another dimension to the work of a diverse group of researchers across The Johns Hopkins University.

The Accelerated Translational Incubator Pilot (ATIP) program has a long name but a streamlined mission: to get promising biomedical innovations to patients faster. ATIP enhances translation of research into new drugs, disease biomarkers, devices or software.

Creating a detailed biological map of the human body was as daunting as any 15th century nautical adventure. But that didn't stop Akhilesh Pandey from assembling a first draft of the human proteome, a “map” of all of the proteins in the human body and an invaluable discovery tool for generations to come.

Like most questions in biology, “Why do we need sleep?” probably has more than one correct answer. Researchers at Johns Hopkins are testing a few theories, each of which tries to explain what goes on in our brains during roughly one-third of each day—activity that is crucial to learning, memory and even life itself. 

Our circadian clock is the invisible hand that brings order to our days, setting the schedule for when we feel alert, sleepy, even hungry. Much is known about the genes and proteins that make the clock, but gaps remain—how, exactly, the clock regulates sleep, for example, and the workings of the brain’s “master clock” that keeps cells in sync. Several Johns Hopkins researchers are working to close the gaps, and they’ve recently made some notable finds.

The human brain, with 100 billion cells forming quadrillions of connections, is at constant risk of missing a connecting flight. And yet, usually, its connections are made accurately and on time. Researchers at The Johns Hopkins University's Department of Neuroscience are working to understand how neural connections are made and how the brain uses them to guide its actions.

In the last decade, physicians and researchers have worked hard to improve treatments for brain cancer patients, finding new ways to deliver drugs directly to the brain and mitigate some of the side effects. 

Neuroscientists have long been puzzled by schizophrenia and autism, and for good reason: Each has a host of genetic and environmental causes. Two Johns Hopkins researchers working to understand the biological causes are Aravinda Chakravarti and Hongjun Song

Neurologist Jeffrey Rothstein studies a wide range of degenerative conditions that affect the nerves and muscles. Rothstein’s team is at the forefront of understanding the molecular changes that precipitate degeneration of the nerve and muscle cells and that eventually lead to clinical disease.

Traumatic brain injuries, whether from physical trauma, stroke or even surgery, are often devastating for patients. Researchers at Johns Hopkins are using a range of approaches to better understand the recovery process and how it might be enhanced.

The advance of technology has rapidly multiplied the questions that scientists can ask and answer in their experiments. These new possibilities make this a time of excitement and promise, but they also bring challenges that must be overcome if the promise is to be realized.

To paraphrase Antony Rosen, the Johns Hopkins University vice dean for research: If science is the pursuit of truth about the material world around us, the most serious crime a scientist can commit is the deliberate falsification of that body of truth.

Here at the school of medicine, misconduct allegations involving the faculty, staff and trainees jumped from two to an average of 16 per year from 2000 to 2012.

Gene sequencing is hot—and for good reason. Genomic data helps researchers decipher everything from the sequenced organism’s susceptibility to disease to genetic tweaks that could make it work better. As a computer scientist by training, Steven Salzberg realized early in his career that computation held the key to answering major questions in genetics.

 

In the research world, the term Valley of Death refers to that place between the lab bench and the marketplace where many good biomedical ideas wither away and die. It exists, in part, due to a gap in funding: Grants from the largest funders of biomedical research generally focus on basic research, but most basic science discoveries require further testing through expensive animal or clinical trials before industry investors will commit.

Gymnasts never practice without someone there to "spot" them---to watch carefully and catch them if they slip. Basic science researchers are in a profession more complex than gymnastics, but they are rarely provided with the coaches they need to spot them. That's something the Johns Hopkins University School of Medicine aims to change with a new course designed to help senior faculty members develop a framework and specific tools for helping other mentors---usually their more junior colleagues-improve their own mentorship.

When working to determine what each of our approximately 20,000 genes do, most researchers turn to mice and other organisms whose genes have a lot in common with ours. Figuring out what a gene does in mice gives investigators a good idea of what the human version does. Using a new technique, researchers at Johns Hopkins and elsewhere are now able to accelerate that process, promising speedier decoding of life's instruction book.

The transposons in your cells are probably identical to those of your parents. These pieces of DNA, also known as transposable elements, can theoretically move or “jump” themselves around the genome, but they stay put most of the time.

A population’s diet, environment and exposure to disease all affect which genes get passed onto the next generation by influencing which individuals survive and are best able to reproduce. When confronted with a deadly disease, for example, a particular gene variant might give a survival advantage to those in the population that happen to have it. 

Clinical trials on Parkinson’s disease drugs must rely on crude clinical assessments of patients’ impairment and symptoms, making them exceptionally large, lengthy and costly. Approved Parkinson’s drugs do exist, but they only treat the symptoms of the disease without affecting its progression. To truly combat the disease, researchers need to be able to measure its severity with biomarkers.

It seems that no scientific society’s annual meeting is complete without an awards ceremony, and charitable foundations and the occasional wealthy individual sometimes promote biomedical discovery by giving out awards. But how are these awardees chosen? It turns out that, at least at Johns Hopkins, the selection process begins earlier than you might think, with a standing committee tasked with making sure that no faculty members and no awards fall through the proverbial cracks.

Toxoplasma gondii is a media-friendly protozoan, and since Robert Yolken began studying it a decade ago, he’s enjoyed more than his 15 minutes of fame. Yolken is happy to expound on the well-known (and sensational) basics: that toxoplasma’s preferred host is a cat and that when it finds its way from cat feces into a mouse or rat it reprograms the rodent’s brain to make it more likely to be eaten by a feline. The parasite also infects humans.

If only I had known then what I know now—that heart cells can beat in a dish without a heart to enliven them—I might not have let the dead man’s lingering heart beat panic me. I might not have so hastily admitted to my most perfect crime. But what could I do? And what can I now do but dedicate my powers to the mission before me? To the instruction of all those who follow—lest my ill-deserved plight befall them too.

Dave Tunkel greets his next patient and has a seat on the edge of his hotel bed. Clad in a Ravens polo shirt and with an otoscope as his only doctorly tool, the Johns Hopkins otolaryngologist chats with the patient about her tinnitus and dizziness. This is not your typical visit to the doctor.

 

In his welcoming remarks to this year's cohort of graduate students at the School of Medicine, the vice dean for education told attendees, “When most people think about a career in science, I think they think that the scientific stage—the place where science is generated—is the lab bench, but that’s wrong, If it were right, it wouldn’t matter if you were at Johns Hopkins or anywhere else doing your research."

An oft-heard refrain is that for tenure-track researchers, it’s very difficult to fit family obligations in among grant applications, research publications, supervising trainees and—oh, yes—research. How true is that of Johns Hopkins? Six scientists share their stories.

If there were a satisfaction survey about the model organism you study, how would you rate it? If our unofficial, random survey (n=5) is at all representative, most of the basic science researchers at Johns Hopkins would be “very likely” to recommend their model organism to undecided graduate students.

Go looking for the Government Affairs office at Johns Hopkins, and you won’t find a smoke-filled room. In fact you won’t find a designated office at all, but rather a handful of spacious cubicles in a vast open space. It’s from this somewhat unlikely looking home base that the Government Affairs team lobbies lawmakers and agencies on issues ranging from research regulation to immigration to Maryland's hospital rate-setting.

 

Knowledge is power, so people can get pretty testy when kept in the dark—especially when it’s about their own genes, and especially when those genes could increase the risk of a disease as high-profile as breast cancer. Maybe Myriad Genetics should have thought about that before choosing to monopolize the tests for BRCA1 and BRCA2, two genes that are responsible for 5-10 percent of all breast cancers and more than 50 percent of hereditary breast cancers.

Before Stephanie Keyaka came to Johns Hopkins for a summer of research, she thought scientists were “strict, mean and all cooped-up.” Instead, she found that Johns Hopkins scientists are “down-to-earth and look just like everyone else walking down the street.” Stephanie grew up in the Johns Hopkins neighborhood but thought of our institution as far removed from her own life. 

What would your reaction be to an email informing you that someone you have never met wants to give you $2,500? Graduate student Kunal Parikh's first reaction was to think that the email was spam. Then he realized it came from the director of his department and his mentors were copied on the message, so the spam scenario seemed unlikely.

Each June, a group of intrepid undergraduate and master’s degree students at Johns Hopkins take on a tough challenge: to work with others to invent a device that would solve a real health care problem in a user-friendly and cost-effective way—all in just one academic year. Those students, participants in the Center for Bioengineering Innovation & Design program, presented the fruits of their labors at the program’s annual Design Day.

Medical research is generally seen as a good thing by everyone, so why rally for it? The impetus for this public show of support for research funding was primarily the infamous spending cuts known as “the sequester,” which went into effect on March 1. Gathered at the rally in front of the Carnegie Library at Mt. Vernon Square were thousands of people, mostly research scientists attending the American Association for Cancer Research’s annual conference at the nearby convention center.

Somewhere along the family tree, small DNA fragments from chromosomes 2 and 6 swapped places. For at least three generations, the rearrangement lay silent, with carriers living normal, healthy lives. But then, in generation four, everything changed. The already misplaced genetic material was unevenly distributed to a gamete that would become a girl, resulting in learning disabilities.

Natalia Trayanova studies broken hearts—that is, hearts that don't work properly due to heart disease. Though Trayanova works closely with cardiologists and watches many of their procedures, the hearts she studies are on a computer screen. Her lab develops computer models of the heart to help clinicians better diagnose and treat heart problems.

MOMA. In this case, it’s not an acronym for New York’s Museum of Modern Art, but rather the Mars Organic Molecule Analyser. It’s the brainchild of one of Johns Hopkins’ very own, Dr. Bob Cotter.

As he tells it, he wasn’t one of those “Star Wars kids” that grew up wanting to explore space. Instead, his fascination lay in tinkering with machines. And he was good at it, too. His forte was building mass spectrometers, complex machines that break molecules into smaller ones carrying electrical charges.

The following story is a biographical sketch of Bob Cotter, a professor of pharmacology and much-loved member of the Hopkins family for more than four decades, who died suddenly last November of heart failure.

Most people, both inside and outside his lab, knew Dr. Robert James Cotter as “Bob”– and nothing else. When his graduate students and postdoctoral fellows introduced themselves at scientific conferences, the phrase “I work for Bob” would elicit palpable respect without need for further identifiers.

The average number of authors on papers included in the Science Citation Index increased by about 50 percent between 1990 and 2010, according to data from Thomson Reuters, which means that middle-author contributions are on the rise. So how important are middle-author contributions when a scientist is up for promotion through the tenure track?

Globalization presents new opportunities for American scientists eager to venture outside U.S. borders.

Research universities such as Johns Hopkins have focused on preparing scientists for academic research, with research positions in industry often being “plan B.” But there aren’t enough jobs in academia to go around.

Despite their ubiquity as research tools, there is still much we don’t fully understand about bacteria — such as how they divide. Learning more could point the way to new desperately needed antibiotics.

In communicating science, words do not always suffice. A picture is worth a thousand words. This aphorism may be particularly relevant in science, where pictures—illustrations, diagrams and other images—can illuminate the esoteric and the complex. 

The next phase of personalized medicine will require intensive computational science, says Feilim Mac Gabhann.

Translating discoveries into products and profits was once a remote aspect of academic research. Not anymore. Many scientists and technology transfer professionals speak about a place called the “Valley of Death.” You won’t find this valley on any map. It’s a metaphorical place that refers to the gap between a scientific discovery and its application in the form of a medical treatment. Innovations often languish in this translational void.

From blood vessels to bronchi, tube-shaped structures are found throughout the body. As plumbers and pasta makers know, the tube is a remarkably practical shape, whether it comes in the form of a pipe or a piece of rigatoni. Tubular architecture is also a recurring theme throughout the human body.

Johns Hopkins and dozens of other research universities are trying a new approach to drug research. Rather than restricting their participation to the fundamental first stage of drug research, the traditional role for academia, these universities are participating in more of the downstream segment. In these programs, veteran drug industry professionals now work shoulder to shoulder with basic scientists.