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Under the leadership of Thomas Hooven, MD, researchers at UPMC Children’s Hospital of Pittsburgh are addressing the problem of serious bacterial infections that affect newborns. These infections can be life threatening and many are associated with long-term complications that create challenges for growing children and their families for years to come.
The Hooven Lab seeks to understand the molecular interactions between babies and bacteria that give rise to these infections. Why do some bacteria cause infections in newborns but rarely in older children and adults? How do babies protect themselves from the many billions of new bacteria that they encounter in the first few weeks of life? Can a better understanding of neonatal immunity help drive new treatments to reduce the burden of serious bacterial infections during this uniquely vulnerable period of life? These are the kinds of questions we seek to answer through molecular and genetic investigations of newborns, bacteria, and their interactions.
Group B Streptococcus (GBS) is the most common cause of neonatal infectious morbidity and mortality in the United States and in many countries around the world. GBS is commonly found colonizing the adult intestine and reproductive tract, but rarely causes serious disease outside of infancy. Around the newborn period, however, GBS can cause serious infections: sepsis, meningitis, pneumonia, and joint infections. While some of the ways that GBS causes newborn infections are understood, unanswered questions remain. Our lab is using bioinformatics, high-throughput approaches, and novel disease models to understand how and why neonatal GBS infections occur.
Group B Streptococcus (GBS) is a normal part of the adult intestinal and reproductive tracts) and can cause infection in newborns through two separate pathways. In early-onset disease (within the first week of life), GBS in the birth canal colonizes the newborn around the time of delivery. In late-onset disease (after the first week), the bacterial exposure occurs in the infant’s environment.
Our lab is using advanced machine learning approaches to predict necrotizing enterocolitis (NEC), a devastating intestinal disease that primarily affects preterm infants. Our strategy uses analysis of the intestinal microbiota, the bacteria that enter and colonize a newborn’s intestine after birth, and which can be isolated from a stool sample collected from the diaper. While the intestinal microbiota varies between individuals and can also change over time, we have developed computational strategies that rely on neural network-driven algorithms to filter signals from noisy data, potentially pointing the way toward new ways to prevent a dreaded newborn illness.
Necrotizing enterocolitis (NEC) is a common, serious intestinal disease that affects preterm infants, usually in the setting of a neonatal ICU. Traditional diagnosis relies on clinical manifestations, which can be subtle and sometimes develop too late to prevent major complications, or X-ray findings, as shown here. The red arrows show air in the intestinal wall, a sign of developing NEC.
The Hooven Lab is working with collaborators from New York’s Columbia University Department of Computer Science to develop a neural network-based predictive algorithm (diagrammed here as a schematic) to identify preterm infants at high risk for NEC using stool microbiota and basic clinical data. Our prototype improves on traditional approaches by generating early, actionable NEC risk predictions without having to wait for disease onset to occur.
Kathyayini Gopalakrishna, MBBS, PhD
Mary Keith, MS, DO
Jordan Elder, BS
Hemanjani Bhavana, MS
The Hooven Lab
UPMC Children’s Hospital of Pittsburgh
John G. Rangos Sr. Research Center, Room 8128
4401 Penn Avenue
Pittsburgh, PA 15224
The Hooven Lab received three awards to study various aspects of Group B Streptococcus (GBS) pathogenesis. An R.K. Mellon Pilot Project Award, a Children’s Trust Young Investigator Award, and a pilot grant from the i4Kids Institute will help us launch new projects intended to understand and prevent GBS infections in newborns. We are grateful and excited!
Our group received R21 funding from the National Institute of Allergy and Infectious Diseases to develop and characterize complete, indexed mutant libraries of GBS. This work will be conducted with the research team of Adam Ratner, MD, MPH, at New York University and in collaboration with Hervé Tettelin, PhD, at the University of Maryland Institute for Genome Sciences.
Together with collaborators Ansaf Salleb-Aouissi, PhD, and Adam Lin of New York’s Columbia University, Dr. Hooven presented work on novel machine learning approaches to predict necrotizing enterocolitis at the virtual Association for Computing Machinery Conference on Health, Inference, and Learning.
Kim F, Polin RA, Hooven TA
2020 Oct 1
Multiple Instance Learning for Predicting Necrotizing Enterocolitis in Premature Infants Using Microbiome Data
Hooven TA, Lin YC, Salleb-Aouissi A
Proceedings of the ACM Conference on Health, Inference, and Learning
Human Herpesvirus-6 in a Premature Infant with Fevers: A Case and Literature Review
Kim F, Reichman V, Hooven TA
Clinical Medicine Insights, Case Reports
2020 Apr 18
A Counterselectable Sucrose Sensitivity Marker Permits Efficient and Flexible Mutagenesis in Streptococcus Agalactiae
Hooven TA, Bonakdar M, Chamby AB, Ratner AJ
Applied and Environmental Microbiology
Evaluating At Risk Newborns for Early Onset Sepsis
Good PI, Hooven TA
Pediatrics Clinics of North America
2019 Feb 1
What’s the harm? Risks and Benefits of Evolving Rule-out Sepsis Practices
Hooven TA, Randis TM, Polin RA
Journal of Perinatology
2018 Feb 26
The Streptococcus Agalactiae Stringent Response Enhances Virulence and Persistence in Human Blood
Infection and Immunity
The Essential Genome of Streptococcus Agalactiae
Hooven TA, Catomeris AJ, Akabas LH, Randis TM, Maskell DJ, Peters SE, Ott S, Santana-Cruz I, Tallon LJ, Tettelin H, Ratner AJ
CD59 Signaling and Membrane Pores Drive Syk-dependent Erythrocyte Necroptosis
LaRocca TJ, Stivison EA, Mal-Sarkar T, Hooven TA, Hod EA, Spitalnik SL, Ratner AJ
Cell Death and Disease
2015 May 28
The Hooven Lab is looking for talented post-doctoral fellows and graduate students interested in infectious disease, bioinformatics, and pediatric outcomes. Please contact Dr. Hooven via email at firstname.lastname@example.org if you are interested.
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