Explore faculty research in the Department of Anatomy and Neurobiology.
Research Focus Areas
Hearing Research Group
Hearing disorders of many types begin in the inner ear, but have long-term effects in the brain. The Hearing Research Group at NEOMED seeks to deepen the understanding of how the central nervous system functions in association with hearing, communication and swallowing, how it is affected by hearing disorders, and how manipulation of the central nervous systems may improve these disorders.
Bone and tissue regrowth is a way for patients to experience complete recovery from previously debilitating conditions such as arthritis, cancer, osteoporosis and bone fractures. The Musculoskeletal Biology Research Group at NEOMED is focused on developing these re-growth processes to address the needs of our aging population.
Dr. Bao’s group focuses on understanding the molecular mechanisms underlying two of the most common forms of hearing loss in the United States. Age-related hearing loss, or hearing loss associated with the aging process, affects roughly half of Americans age 75 years and older, and noise-induced hearing loss, or hearing loss caused by excessive exposure to loud noise, impacts roughly 26 million adults between 20 and 69 years of age. One major cellular mechanism, cochlear synaptopathy, underlies both hearing disorders. Cochlear synaptopathy refers to the loss of synapses, or connections, between sensory cells in the cochlea (the inner ear) and the neurons that transmit sound signals to the brain. Because the sensory cells themselves aren’t damaged under certain conditions, cochlear synaptopathy can’t be detected in a typical hearing test, yet it is the probable reason that some people with reportedly normal hearing thresholds have difficulty understanding speech in environments with a high level of background noise. Dr. Bao’s group develops new functional and molecular technological platforms to study cochlear synaptopathy in both preclinical and clinical models. Because one hearing disorder, tinnitus, is closely associated with hearing loss, and that manifests as a perceived ringing, roaring, clicking, or buzzing in the ears in the absence of an external source of sound. Dr. Bao’s group is also developing tools to detect tinnitus in both rodent and primate models, and further to determine a possible link between tinnitus and synaptic changes, or plasticity, in a part of the brain known as the hippocampus. Currently, no medications have been found to treat any of the above three disorders. Through their research, Dr. Bao and his team are ultimately working to develop new therapies for the treatment and prevention of the most prevalent and debilitating hearing disorders affecting Americans today.
The Cooper Lab investigates age-related changes in the skeletons of long-lived bats. Bats as a group are unique in that their bones bend with wingbeats and they display superb resistance to fracture. The Cooper Lab is currently investigating how bats maintain and renew this flexible matrix for bioengineering applications. In addition, the Cooper Lab’s molecular, biomechanical and structural results shows that bats are unusual in that their wing bones lack age-related bone fragility. The Cooper Lab is currently investigating the molecular mechanisms driving the prevention of age-related bone fragility in bats. Genes of bats that were identified as critical to the maintenance of bone integrity in bats replaced those of mice in cell culture studies. The Cooper Lab aims to modify the cells of elderly mice such that they produce a more youthful bone matrix that lacks vulnerabilities that typically lead to fragility diseases.
The major focus of our research is tinnitus, the sensation of hearing a sound when no external sound is present. Almost all individuals experience this sensation for brief, unobtrusive periods. However, chronic sensation of tinnitus affects approximately 17% of the general US population. People with severe tinnitus may have trouble hearing, working and sleeping. Despite its ubiquity, the pathophysiology of tinnitus is poorly understood, and there is no FDA approved cure or treatment. Using the mouse tinnitus model which we have developed in our laboratory we study brain mechanisms responsible for tinnitus induction following an acoustic trauma. For our research we use a wide variety of techniques spanning from recording of electrical activity in single neurons extracellularly as well as intracellularly to behavioral approaches of tinnitus assessment using gap-induced inhibition of the acoustic startle reflex.
We thank the National Institute for Deafness and other Communication Disorders for their support of this work.
Swallowing difficulties, and the failure to protect the airway, are a major cause of health problems in premature or preterm infants. The neurological cause for these problems is unknown, and as a result there are few effective therapies. In our lab we work on understanding the biomechanics and pathology of neural control of swallowing using an animal model, the baby pig. Understanding the mechanism of airway protection failure will provide a biological basis for decisions about care and intervention in these fragile and cherished patients.
Another focus in the lab is the impact of Parkinson’s disease on feeding, swallowing, and airway protection. Such patients suffer from many effects of compromised eating, such as reduced nutrition and chronic aspiration. These problems hard to diagnose because patients do not report them and they require invasive imaging to be seen. In collaboration with Dr. Jason Richardson, we are carrying out animal model, integrative studies from brain to tongue and jaws, to determine what is going wrong, and how it can be fixed.
Professor of Anatomy and Neurobiology
Dr. Haqqi’s group focuses on developing new treatment modalities for degenerative joint diseases such as Osteoarthritis. Aging is a major factor for chronic diseases including osteoarthritis, a leading cause of joint dysfunction associated with cartilage
degradation, disability and poor quality of life in the affected population worldwide. Among adults 60 years of age or older the prevalence of symptomatic knee osteoarthritis is approximately 10 percent in men and 13 percent in women. There are no disease-modifying medical therapies currently available for osteoarthritis. The ultimate objective of our research program is to address this unmet need, by identifying and validating novel compounds and their target molecules in chondrocytes, the only cell type present in the cartilage, that can inhibit induction and/or limit the progression of osteoarthritis. In addition, the group is also studying epigenetics in cartilage and the potential of plant derived inhibitors that will be most effective in suppressing joint damage. These research projects are funded by the NIH/National Institutes of Arthritis and Musculoskeletal Diseases and the NIH/National Center for Complementary and Integrative Health.
Evolutionary Morphology of Bird Wings
My research aim is to understand the musculoskeletal anatomy and function of bird wings. Birds have dramatically altered the common components of the forelimb to respond to the functional demands of flight. Within this system, my research addresses three basic questions: (1) what are the morphological adaptations that allow birds to fly so efficiently (or, what can we learn from birds about building wings)? (2) how have birds modified basic tissues such as bone and ligament to adapt to new forms of loading (what can bird bones teach us about material design)? (3) how has the evolution of different avian flight styles and capabilities played out over evolutionary time (some wing morphology is adaptive for specific types of flight, some may be phylogenetic inertia—which parts are which)? My lab addresses these questions using novel techniques that bridge the gap in scale between standard gross anatomy and histology, as well as modeling and analysis approaches that allow us to leverage the diversity of living and fossil birds as a broad pool of natural experiments.
We investigate the cellular mechanisms of auditory processing, with a focus on neuromodulation under normal hearing and hearing-impaired conditions. Electrophysiological (e.g. whole-cell recordings) and optical imaging (e.g. calcium imaging) approaches, combined with pharmacological immunohistochemistry tools, are employed. We aim to provide a basic understanding of neuromodulation in functionally well-established auditory circuits that analyze information for sound localization. Ultimately, this will provide the basis for therapeutic intervention in hearing disorders characterized by impaired sensitivity to precise temporal features in sounds.
We study how the neural circuits in hearing change as we age. Age-related hearing loss is associated with a reduction in the level of GABA, a key neurochemical used to communicate among neurons throughout the auditory system. The loss of GABA leads to a variety of hearing deficits, including impairment of the ability to detect fine differences in the timing of sounds.
My laboratory identifies the auditory circuits particularly susceptible to GABA loss during aging, using complex circuit-tracing, immunohistological and imaging methods.
Associate Professor of Anatomy and Neurobiology
Project 1: Histology Curriculum Project: “Histology Across the Human Lifespan: A Photographic Atlas Project”
The electronic photographic atlas will guide students in the identification of predictable microscopic changes that occur in human tissues across the lifespan of an individual. The images and curricular activities will prepare students to recognize disruptions in the sequence and/or timing of these age-normal histological changes as pathological indices for medical intervention.
Students examine microscopic samples of the same tissue type from individuals of different ages that include a pediatric exemplar, an adolescent exemplar, plus adult and geriatric samples. In addition, this atlas project will provide comparisons of adult tissue exemplars from all major organs between individuals with a normal body mass index (BMI) and those with an abnormally high BMI. Individuals with a BMI >30 are considered obese, and are at-risk for serious health complications. Laboratory exercises embedded in the electronic atlas will be designed to actively engage students in the analysis and interpretation of profound tissue changes that can occur in obese individuals.
Project 2: Do Spatial Skills Influence Outcomes on Standardized Entrance Exams for Undergraduate Healthcare Majors?
Spatial skills have been shown to be correlated with performance in scientific fields. These skills may be particularly important to high achievement in medical school, where the extrapolation of 2D images to 3D patients is increasingly important for diagnosis and treatment monitoring. Subsets of students, like females, those of lower socioeconomic status and first generation college students have been shown to score lower on specific tests for spatial skills. We are interested in determining whether spatial skills are correlated with scores on standardized entrance exams for a wide variety of healthcare professional/post-baccalaureate programs (MCAT, DAT, OAT, PCAT, etc.). From an ongoing pilot study conducted at NEOMED 2014 – 2017, we have initial data that suggest this relationship may exist – at least for medical students and pharmacy students from various undergraduate institutions that NEOMED students matriculate from. In addition, we are interested in offering interested students access to free on-line spatial skills training to see if there spatial skills improve on a widely- recognized spatial skills test. Lastly, we would like to know if students who have undertaken spatial skills training score higher on a standardized entrance exam compared with an age/gender matched peer who had the same original spatial skills score as the spatially-trained student.
Early hearing loss is a risk factor for later problems with speech processing due to changes in auditory brain regions, and early stress exacerbates these deficits. Our laboratory studies how early hearing loss and stress can change auditory perception related to speech, and its underlying neural circuits. We use behavioral, neurophysiological, neurochemical, anatomical, and computational techniques to measure how neural activity and circuitry are altered by these developmental disorders, and how neural changes correlate with deficits in learning and perception. We measure neural responses to vocal communication and to natural and artificial sounds in the Mongolian gerbil, using implanted electrode arrays or intracellular recordings, where we can manipulate neurochemicals to assess circuit contributions to neural responses. We test animal perception using a variety of behavioral tasks, including operant conditioning and acoustic startle. This work lets us identify interventions that remediate perceptual deficits arising from these early experiences, in addition to understanding their underlying causes.
Regulation of bone cell development and function, with specific emphasis on growth factors that can enhance osteogenesis
Bone loss is a major health care problem in the United States and worldwide. Risk factors associated with osteoporosis, include estrogen-deficiency (post-menopuasal) and aging. During bone development and its maintenance, the antagonistic processes of bone formation and resorption are regulated by various systemic and local factors (hormones, growth factors, cytokines, etc). It is evident that bone formation during skeletal modeling/remodeling and fracture repair requires stringent control of osteoblast proliferation and differentiation. Regulation of these biological processes involves sequential expression of cell growth and tissue specific genes in response to different regulatory signals.
Dr. Safadi’s research laboratory focuses on the regulation of bone cell development and function, with specific emphasis on growth factors that can enhance osteogenesis. We are interested in various metabolic bone diseases such as age/estrogen-induced osteopenia, osteopetrosis and cartilage-associated diseases (osteoarthritis and rheumatoid arthritis). The goal of our research is understand the pathological mechanisms underlying various bone diseases in order to develop strategies for the therapeutic management of such diseases. We identified a novel growth factor (named Osteoactivin) that has anabolic effects on bone. If we understand the mechanisms responsible for this effect, then this factor could be used as potential therapeutic agent to stimulate bone formation in diseases associated with osteopenia, increased risk of fracture and spinal fusion.
In addition, we developed an interest on the role of osteoactivin (gpnmb) as a neuroprotective factor for neurodegenerative diseases such as Parkinson’s disease and Alzheimer disease. This research is conducted in collaboration with the neurodegenerative research group at NEOMED. We also interested on the role of gpnmb as anti-inflammatory factor in acute and chronic conditions for wound healing and neuroinflammation.
Dr. Safadi’s laboratory is also working on another collaborative research with Dr. Mary Barbe at Temple University School of Medicine. Dr. Barbe laboratory utilizes an in vivo model for cumulative trauma disorder that focuses on the molecular and cellular mechanisms associated with tendonitis and inflammation-induced bone loss.
We study brain circuits that modulate how we hear. Such modulation allows us to maximize sensitivity when we need to hear a faint sound (Was that your phone?), filter out noise when we want to hear a friend’s voice in a noisy restaurant, or ignore irrelevant sounds (but not important ones!) when we’re trying to sleep. Acetylcholine is a neurotransmitter that plays a role in these and many other aspects of hearing, helping the brain adapt during normal development, during aging and in response to damage of the ear or brain. A goal of our research is to understand modulation of hearing and how acetylcholine circuits contribute to these tasks.
We study hearing circuits in guinea pigs, rats and mice. We combine the latest techniques using replication-deficient viruses and transgenic animals with classical anatomical tracing and immunohistochemistry to label specific neural pathways. We examine these pathways with light and electron microscopes to identify the cell types and their synaptic connections and thus characterize the brain circuits that allow us to hear.
Mammalian Anatomy, Development, and Evolution
Dr. Thewissen’s research centers on the anatomical specializations of whales and combines gross anatomical, histological, embryological, and paleontological methods. The evolution of whales from living on land to living in water as well as the biology of Arctic whales are central stage in the research program. Examples of specific projects include studying whether living whales are deaf by counting nerve cells in their ears, figuring out how old a whale is by studying tree-ring like structures in the skull, and using the fine structure of the teeth to learn about the biology of the animal. Much of the research is based on fossil whales from Pakistan and India, and samples of modern whales from the Alaskan Arctic, both unique resources.
Evolutionary and Functional Morphology of the Mammalian Skull
My research aims to understand the relationships between the form, function and evolution of the mammalian head. Specifically, I aim to better understand how certain activities, such as chewing or biting, affect the form and evolution of the skull and face. Most of this work is question driven and falls into one of three research avenues: 1) Physiology and functional morphology, 2) Behavioral and ecological morphology and 3) Comparative morphometrics.
A major component of my research involves studying the physiology of chewing and biting. This involves using in vivo methods, such as electromyography, strain gage approaches and video analysis, to study jaw-muscle activity patterns, facial bone strains and jaw movements during chewing and biting in living animals.
A second research focus involves conducting field studies of primate chewing and biting. In addition to allowing us to assess how well our lab research mimics natural field conditions, this work provides an environmental context for interpreting morphological adaptations in the mammalian head. Recent field work includes studying feeding behaviors in free-ranging howling monkeys at Hacienda La Pacifica, Costa Rica.
Finally, I am interested in comparative analyses of skull and jaw-muscle form among mammals. These comparative studies complement the lab and field research by broadly describing patterns of form-function associations and morphological integration among species and/or age-groups.
Our laboratory studies neural mechanisms underlying hearing and acoustically guided behaviors, particularly social communication. We have focused increasingly on interactions between hearing and emotions. Much of our current work examines three facets of these interactions: the link between vocal signals and an animal’s emotional state, the analysis of social vocalizations by emotional centers in the brain, and the manner in which emotional centers modify processing of sounds by the auditory system. We use a wide variety of approaches in our work—acoustic, behavioral, neurophysiological, pharmacological, and anatomical. We are particularly excited about technical developments that will allow us to analyze the activity of individual neurons during social interactions. Our work on the basic neural mechanisms forms the basis for future studies of disorders of acoustic communication that involve misinterpretations of the meaning of sounds.
We thank the National Institute for Deafness and other Communication Disorders for their support of this work.
Research in the Young Lab focuses on evolutionary, comparative and developmental aspects of mammalian locomotion. Our work is question driven and is currently concentrated on two topics: the biomechanics of arboreal locomotion, particularly in primates, and the interaction between musculoskeletal growth and locomotor development.
A principal focus of the work in the lab has been the biomechanics of arboreal locomotion in primates. The aim of this work is to relate standard biomechanical measures – including gait patterns, joint postures, limb forces and center of mass movements – to fitness-critical variables such as balance, accelerative capacity and energetic efficiency. A variety of techniques are used to address this aim, including three-dimensional motion tracking, measurement of single-limb kinetics and whole-body mechanics using custom-designed force transducers, and morphometric assessments of musculoskeletal anatomy. Our current research focuses on using state-of-the-art techniques to quantify locomotor kinematics in free-ranging primates moving in their natural habitats.
A second focus of our research in the lab has been the degree to which growth and development might be adaptively constrained to promote fitness across the lifespan. Immature mammals must often compete against adults for resources, evade common predators and keep pace during group travel, despite small body size, an underdeveloped musculoskeletal system and other limits on performance. We should expect strong selection for mechanisms that permit young individuals to overcome such limitations and reach reproductive maturity. Previous research has examined how allometric changes in skeletal form and locomotor mechanics might facilitate improved locomotor performance in young mammals. Our current research i is focused on how natural selection has impacted growth and locomotor development in cottontail rabbits, a model system representing fast-growing ecologically challenged mammals.
Assistant Professor of Anatomy and Neurobiology
The ability to localize sounds is critical to survival for most animals and in humans facilitates selective attention. The location of sound sources must be computed in the central auditory system from basic frequency, timing, and intensity information. Our brain extracts cues for horizontal (azimuth) sound source location through parallel processing of this information in specialized brainstem nuclei. Because of the strong evolutionary pressure on sound localization ability, the neurons in these nuclei have acquired astounding cellular adaptations that underlie their functional roles within these circuits. Our lab seeks to understand the cellular components of sound localization circuits and how they are sculpted by sound driven activity during development using electrophysiological and imaging approaches. Neurons receive many of their synaptic on tree-like structures called dendrites. However, dendrites do not just passively receive signals. Their physical structure and ion channel composition determines how synaptic signals interact thus determining the input/output transformations of the neuron. We study signal processing in dendrites using dual dendritic patch-clamp combined with multiphoton imaging techniques.
Research Scientist, Anatomy and Neurobiology
Why does hearing your name in a crowded room grab your attention? How can someone sleep through noise from a nearby highway, but be immediately awakened by soft cries from a baby? Why do you start to hate your favorite song if you use it as an alarm for too long? Our work seeks to lay the foundations to answer questions like these about how the brain processes sounds. I focus on three main areas of neuroanatomical research in the auditory system: inhibition, neuromodulation, and descending pathways. Each of these areas contribute to answering the questions above in their own ways, and I use a “big picture” approach to auditory neuroanatomy in my research, with a focus on combining nucleus-specific findings and circuit-level analysis.