Research Projects:
Dr. Malwina Czarny-Ratajczak investigates the contribution of dysfuntional telomeres to primary osteoarthritis. Her project is focused on the molecular consequences of accelerated telomere shortening on transcriptome and proteome of patients with primary osteoarthritis. She studies how these changes affect tissue homeostasis of the knee joint and lead to premature cartilage aging. A better understanding of the molecular mechanisms involved in pathogenesis of primary osteoarthritis will help to develop new methods of prevention and treatment for this disorder, which is the leading cause of pain and chronic disability in the aging population.
Dr. Kristin S. Miller studies how soft tissues grow and remodel. The study of tissue growth and remodeling can identify the key mechanisms of age-related changes and healing deficiencies in soft tissues. The long-term goal of her work is to alter the clinical paradigm for age-related changes in tendons by identifying the significant mechanisms of tendon dynamics before and after injury. Accomplishing this will permit the rational design of clinical intervention strategies to impede tendon degeneration and improve healing.
Dr. Mimi Sammarco investigates the failed regeneration of soft tissue and bone in the context of aging. Dr. Sammarco uses the mouse digit regeneration model to gain a more thorough understanding of how the role of oxygen and cellular metabolism affect regeneration in an aged model in order to delineate between regeneration-competent and incompetent tissue environments. Using aging as a model to better understand regeneration will enable us to shed light on the regenerative process and to develop ways to address fracture healing and poor wound closure in the aged population.
Dr. Hong Liu studies the underlying causes of aneuploidy-driven processes and diseases, such as aging and cancer. Aneuploidy contributes to aging and the development of cancer. It is usually derived from chromosome missegregation during mitosis. Therefore, a better understanding of the mechanisms that control chromosome segregation would help decipher the causes of aneuploidy and as well as its associated aging and cancer. Using a combination of biochemical, cell-biological and genetic tools, Dr. Liu is currently studying 1) the regulation of sister-chromatid cohesion that is critical for proper chromosome segregation, 2) how aberrantly-regulated sister-chromatid cohesion results in aneuploidy, and 3) how aneuploidy contributes to cell senescence, a good in vitro system to uncover the mechanisms of aging.
Dr. Namita Rout is studying the association between chronic systemic inflammation of aging or “inflammaging” and intestinal barrier functions utilizing the nonhuman primate model of rhesus macaques. Inflammaging phenotype is a highly significant risk factor for both morbidity and mortality in the elderly people. Dr. Rout’s research focuses on identifying immune mechanisms underlying the similarities between inflammaging and the unresolved chronic inflammation of antiretroviral drug treated HIV infection, which contributes to the acceleration of comorbidities and frailty in HIV-patients. Understanding the role of intestinal immune cell subsets in the disruption of healthy mucosal barrier function and persistent inflammation will help develop novel therapeutic interventions to target inflammation in aging individuals.
Stem cells respond to their immediate microenvironment to proliferate, differentiate or synthesize matrix proteins as one of the primary mechanisms by which the body regenerates damaged tissues. It is known that the mechanical environment is critical for cellular function in certain tissues; yet, it is unclear how stem cells respond to those cues and how this changes with age. Dr. Taby Ahsan has found that applying mechanical input can direct stem cell differentiation, that this mechanoresponse is mediated by the balance of force inside and outside the cell, and that these types of cues can directly influence the regenerative potential of cells.
Dr. Edward Golob identified two distinct neurophysiological mechanisms in the brain that may underlie age differences in spatial attention control, and also found preliminary evidence that individual differences in higher-level cognition buffered the effect of aging. This expands knowledge of how attention is allocated over space and how it is controlled in real-time, and bears on the role of attention in various theories of cognitive aging. He has been relating these mechanisms to cognitive reserve, which has public health importance because it helps maintain independent living and possibly mitigates the impact of incipient age-related neurological disorders such as Alzheimer’s disease.
Dr. Sangkyu Kim studies the hereditary elements that contribute to healthy aging and longevity. The study of these genetic and epigenetic factors will help identify underlying biological pathways. Knowledge gained through this project may benefit the public by providing awareness of biological and environmental contributions to healthy aging. Knowledge of environmental modulators of healthy aging will prompt lifestyle changes that promote public health. Identification of genetic and epigenetic factors and their biological pathways may lead to healthy aging interventions.
pathogenesis. TGFβ1 is known to be key driver of this disease, but it is unclear how its effects on lung aging are mediated.
Dr. Cecilia Sanchez has discovered an association between sirtuin 1 and 3 signaling and changes in mitochondrial metabolism and cellular homeostasis during myofibroblast differentiation, a hallmark of pulmonary fibrosis. This research will lead to therapies to delay or treat lung fibrosis and improve organ function in the elderly.
Dr. W. Lee Murfee established a new tool for microvascular research that enables probing of multi-cell interactions during angiogenesis. The model allows for time-lapse imaging of the same microvascular network during angiogenesis and investigation of pericyte-endothelial cell interactions at specific vessel locations within a real network - capabilities which do not exist in current angiogenesis models. Application of this rat mesentery culture model provides a simple and unique method for screening the effectiveness of pro- or anti-angiogenic therapies on real, intact microvascular networks and thus reversing age-related increases in microvasculature resistance.
Dr. Andrea Zsombok has collected exciting preliminary data indicating that activation of autonomic brain circuitry contributes to the regulation of systemic glucose levels. Her studies focus on the contribution of TRPV1 to the regulation of glucose homeostasis and the consequences of diabetes on the system. Obesity and diabetes are of increasing significance with aging; therefore, exploring novel mechanisms can lead to alternative strategies to improve glucose homeostasis through centrally directed therapies.
Through COBRE funding, the core has expanded its instrumentation under the leadership of Dr. Malwina Czarny-Ratajczak, with the purchase of the Ion Proton next-generation sequencing system. This augments existing equipment, including ABI3130xl sequencers, Illumina Beadstation GX, ABI7300 real-time PCR machine, and others. Dr. Leann Myers is the core biostatistician. This Core collaborates closely with the Next-Generation Sequence Data Analysis Core lead by Dr. Erik Flemington in the Cancer Genetics COBRE at Tulane University.
