Bioengineering welcomes new faculty Jensen and Lam
Recently, Bioengineering welcomed two young assistant professors to the department—Paul Jensen and Fan Lam—who will make important contributions to, respectively, MR spectroscopic imaging in neuroscience and computational genomics for microbial health.
Studying the bacteria affecting pediatric and oral health
Part of everyone's microbiome, the streptococci are bacteria present in the mouth, upper respiratory tract, intestines, and on the skin. These microbes are responsible for tooth decay and infections like strep throat, pink eye, scarlet fever, and meningitis. "Strep live on your body all the time," said Illinois Bioengineering Assistant Professor Paul Jensen. "When you get an infection from strep something has gone out of control. My research group studies how strep interact with all other bacteria and how bacterial imbalances cause disease."
A Bioengineering faculty researcher since 2016, Jensen became a tenure-track faculty member in August 2018. He also is a researcher at the Carl R. Woese Institute for Genomic Biology on campus.
Jensen and his research group study why and how bacterial communities become imbalanced and cause disease. Looking specifically at the Streptococcus mutans and Streptococcus sobrinus bacteria that cause cavities, they have built a metabolic model and analyzed the network that drives their physiology.
Through experimentation and computational modeling, they have discovered that when the bacteria are stressed—exposed to antibiotics, for example—they randomly turn genes on. "The bacteria look like they have no clue what they are doing," explained Jensen, noting that anti-biotics have been in use for less than 100 years. "They just randomly turn on genes, possibly hoping that this will help them out because they are experiencing something that hasn't been with them as they evolved."
On the other hand, Jensen said, when bacteria are starved of nutrients they know exactly which genes to activate. According to Jensen, this likely occurs because strep have evolved and learned to adapt to recurrent starvation over thousands of years.
Jensen and his team utilize their models to try and answer big-picture questions about how the microbe interact with stressors, as well as the surrounding bacterial communities. When the models yield interesting results, they then conduct experiments in the lab.
Groundbreaking sequencing work
His group has recently sequenced the entire genome of S. sobrinus, which when combined with S. mutans, causes rampant tooth decay in certain people. This work is a significant advance since a complete genomic profile did not yet exist for this particular microbe. (The S. mutans genome was sequenced in 2002 and researchers have a much more in-depth knowledge about it. Most dental research focuses on S. mutans.)
The complete genome allowed Jensen to answer a longstanding question about S. sobrinus. Researchers have long suspected that S. sobrinus has an incomplete pathway for quorum sensing, which is the ability bacteria have to sense and react to nearby bacteria. The new sequences confirm that some quorum sensing genes are nowhere to be found. "We're not really sure why this is or what the consequences are, but we’re exploring several possibilities with our mathematical models," Jensen said.
Advancing MRSI technology
Bioengineering Assistant Professor Fan Lam is developing and applying advanced magnetic resonance (MR)-based techniques to more accurately map the molecular information in the brain. The ability to map and quantify molecular fingerprints of neural tissues would have significant impact on the study of the physiological basis of brain functions and neurodegenerative diseases, early diagnosis of central nervous system disorders, as well as accurate monitoring of treatment efficacy on these diseases.
MRI has been established as an essential tool to probe the brain’s anatomy and function by imaging the water molecules, but Lam is working to extract additional information from the MR signals, and enable researchers to visualize detailed spatial and temporal variations of many different molecules in the brain, which are involved in various important physiological functions and are altered in specific diseases and their subtypes.
“My research focuses on developing imaging tools to visualize these molecules in the brain non-invasively,” Lam said. “Specifically I’m developing a set of MR spectroscopic imaging (MRSI)-based technologies which will allow us to detect and quantify these molecules without the need of injecting any contrast agents into the body.”
MRSI has been used to study metabolic changes in the brain as well as other organs. “The main challenges for achieving such label-free molecular imaging using MRSI lie in the facts that these molecules typically have three to four orders of magnitude lower concentrations than water molecules—existing imaging methods to acquire their information are very slow, preventing them from being practically useful,” Lam said.
To address these challenges, he has dedicated his research to the development of new models, data acquisition strategies, and quantitative analysis and computational tools to address the speed, resolution, and sensitivity challenges for MRSI—and its integration with other neuroimaging technologies to study brain functions at normal and diseased states.
Lam, who earned his master’s and doctoral degrees in electrical and computer engineering (ECE) at Illinois, was named a Beckman Graduate Fellow in 2012, working with Zhi-Pei Liang, a professor of ECE, and Brad Sutton, a professor of bioengineering—both members of the Bioimaging Science and Technology Group (BST).
Development of SPICE
With Liang and his students, Lam has already contributed to the development of what is considered an important advance in MRSI technology: SPICE (spectroscopic imaging by exploiting spatiospectral correlation). In development by Liang’s group for more than a decade, the new approach addresses fundamental technical challenges in MRSI using novel signal generation, encoding and decoding methods developed within a subspace imaging framework.
“Fan is an outstanding researcher; he is one of those rare talents that a professor may encounter once in every 10 years or so,” Liang said. “I was very pleased to have recruited him to my group and he has exceeded all my expectations, making important contributions to our solution of the long-standing problems associated with MRSI.”
Through his postdoc fellowship, Lam has elevated SPICE even further and established a new technological framework for achieving rapid, ultrahigh-resolution MRSI. “Now we are able to achieve whole brain mapping of a number of metabolites in just five minutes with resolution matching that of a standard functional MRI scan. This is already more than an order of magnitude improvement over any existing methods,” Lam said. “My goal is to make simultaneous metabolite and neurotransmitter mapping, and comprehensive metabolic profiling of neural tissues into reality. I believe that with our recent progress these goals are within reach. Accomplishing them would lead to early diagnosis of diseases, better and more efficient treatment, and more importantly, move us toward the goal of better understanding the molecular basis of brain function and diseases.”
Lam also acknowledges the colleagues from Liang’s group whom he has been collaborating with, including Chao Ma, a former Beckman Postdoc Fellow who is now a faculty member at Harvard Medical School and Massachusetts General Hospital in Boston; Xi Peng, a former Beckman visiting scholar; and graduate students, Bryan Clifford, Rong Guo, Yudu Li, and Yibo Zhao. “I feel very fortunate that I was able to work closely with these motivated and talented researchers. Their valuable contributions helped make SPICE possible.”
Lam’s research also is looking at incorporating machine learning into the imaging process. He has developed an algorithm that takes advantage of known spin physics, biochemistry, and extensively available low-resolution spectroscopy data to derive prior information that can be used in quantitative metabolic imaging studies using MRSI. In addition, his collaborative research has demonstrated the feasibility of simultaneous quantitative susceptibility mapping (QSM) and metabolic imaging of the brain using SPICE-based techniques, which could offer a wide range of applications including the study of brain metabolism and neurodegenerative diseases.
His advancements may impact a range of neuroscience studies in Beckman and across campus. He is working with BST members Ryan Dilger, a professor of animal sciences, and Austin Mudd, a graduate student, on a nutritional study using neuroimaging to look at how iron deficiencies in piglets affect brain development and determine if iron supplementation later in life can improve brain function. This study has been published in the journal Nutrients.
He also has an ongoing collaboration with Aron Barbey, an associate professor of psychology, using SPICE to image patients with traumatic brain injury (TBI). “We need to have a way to measure brain function to give a more accurate diagnosis and prognosis. It has been shown that the metabolic information is very helpful in terms of accessing tissue damage and predicting how the patient recovers. We hope by integrating our joint susceptibility and metabolite mapping technique into a multimodal neuroimaging protocol, we will be able to identify new biomarkers for the diagnosis and treatment of traumatic brain injury,” Lam said.
Having access to facilities at Beckman has helped advance Lam’s research. “BIC is an amazing facility with strong technical support,” Lam said. “I work very closely with the people in BIC. And the neuroimaging expertise and exciting research from faculty members like Sutton and Barbey also attracted me to the Beckman community.”
As a Bioengineering faculty member, Lam will continue the collaborative relationships he has developed that help further his goals and find new applications for these imaging techniques. He also aims to establish a new collaboration with the Carle Illinois College of Medicine to develop and translate new molecular imaging technologies to study specific neurodegenerative diseases and assess the effectiveness of treatments.