ANTHONY JOHN DONATO

Associate Professor, Department of Internal Medicine, Division of Geriatrics

Adjunct Associate Professor, Departments of Biochemistry and Nutrition and Integrative Physiology

Click Here for Dr. Donato’s CV

Office Address:

VA Med. Center, SLC
GRECC, Building 2, Room 2D15A
500 Foothill Drive
Salt Lake City, UT 84148
Office: 801-582-1565 Ext 4237
Lab: 801-582-1565 Ext 4331
Cell: 619-701-1744
Email: tony.donato@utah.edu

Research Interests:

My primary research focus is vascular aging, in particular the cellular, molecular and tissue specific events that induce reductions in muscle blood flow during exercise, impair arterial endothelial function and stiffen large elastic arteries in older rodents/adults. These vascular phenotypes contribute to the age-related decline in functional capacity and the development of cardiovascular disease. My secondary focus, is to elucidate the cellular pathways which confer the vaso-protective effects of these lifestyle interventions and try to activate these pathways pharmacologically to see if this will confer some of the same benefits. I have used human, rodent, and cell models to address these questions and utilized a wide range of contemporary translational experimental techniques from microRNA gene expression to ultrasonography to investigate the aforementioned interests.

Selected Publications:

Morgan RG, Ives SJ, Lesniewski LA, Cawthon RM, Andtbacka RH, Noyes RD, Richardson RS, Donato AJ(2013). Age-related telomere uncapping is associated with cellular senescence and inflammation independent of telomere shortening in human arteries. Am J Physiol Heart Circ Physiol, 305(2), H251-8.Donato AJ, Walker AE, Magerko KA, Bramwell RC, Black AD, Henson GD, Lawson BR, Lesniewski LA, Seals DR (2013). Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice. Aging Cell, 12(5), 772-83.Gano LB, Donato AJ, Pasha HM, Hearon CM Jr, Sindler AL, Seals DR (2014). The SIRT1 activator SRT1720 reverses vascular endothelial dysfunction, excessive superoxide production, and inflammation with aging in mice. Am J Physiol Heart Circ Physiol, 307(12), H1754-63.Gibson CC, Zhu W, Davis CT, Bowman-Kirigin JA, Chan AC, Ling J, Walker AE, Goitre L, Delle Monache S, Retta SF, Shiu YT, Grossmann AH, Thomas KR, Donato AJ, Lesniewski LA, Whitehead KJ, Li DY (2015). Strategy for identifying repurposed drugs for the treatment of cerebral cavernous malformation. Circulation,131(3), 289-99.Walker AE, Henson GD, Reihl KD, Morgan RG, Dobson PS, Nielson EI, Ling J, Mecham RP, Li DY, Lesniewski LA, Donato AJ (2015). Greater impairments in cerebral artery compared with skeletal muscle feed artery endothelial function in a mouse model of increased large artery stiffness. J Physiol, 593(8), 1931-43.Frech T, Walker AE, Barrett-O’Keefe Z, Hopkins PN, Richardson RS, Wray DW, Donato AJ (2015). Systemic sclerosis induces pronounced peripheral vascular dysfunction characterized by blunted peripheral vasoreactivity and endothelial dysfunction. Clin Rheumatol, 34(5), 905-13.Walker AE, Morgan RG, Ives SJ, Cawthon RM, Andtbacka RH, Noyes D, Lesniewski LA, Richardson RS,Donato AJ (2016). Age-related arterial telomere uncapping and senescence is greater in women compared with men. Exp Gerontol, 73, 65-71.Beyer AM, Freed JK, Durand MJ, Riedel M, Ait-Aissa K, Green P, Hockenberry JC, Morgan RG, Donato AJ,Peleg R, Gasparri M, Rokkas CK, Santos JH, Priel E, Gutterman DD (2016). Critical Role for Telomerase in the Mechanism of Flow-Mediated Dilation in the Human Microcirculation. Circ Res, 118(5), 856-66.

LISA LESNIEWSKI

Associate Professor, Department of Internal Medicine, Division of Geriatrics

Adjunct Associate Professor, Department of Nutrition and Integrative Physiology

Click Here for Dr. Lesniewski’s CV

Office Address:

VA Med. Center, SLC
GRECC, Building 2, Room 2D08
500 Foothill Drive
Salt Lake City, UT 84148
Office: 801-582-1565 Ext 4-2046
Lab: 801-582-1565 Ext 4-3361
Email: lisa.lesniewski@utah.edu

Research Interests:

The age of the US population is steadily increasing as is the prevalence of overweight and obesity, and both aging and obesity are primary risk factors for cardiovascular and metabolic diseases. My laboratory’s broad research interest is to understand the mechanisms underlying vascular and metabolic dysfunction and disease with advancing age as well as to understand how this is exacerbated by overweight/obesity.

Ongoing Research Projects:

Effects of Aging and Obesity on the Adipose Tissue and its Vasculature:

While once thought of as a merely a storage site for energy, the adipose tissue is now recognized as an endocrine organ that plays a central role in metabolic dysfunction in obesity. The adipose also demonstrates dysfunction with advancing age and may contribute to both vascular and metabolic disease by dysregulating lipid handling and contributing to systemic inflammation.

My laboratory is interested in elucidating both the role that adipose tissue dysfunction may play in age-associated vascular and metabolic dysfunction and the mechanisms by which aging and obesity lead to dysfunction in the adipose tissue and its associated vasculature. In particular, we are exploring the role of telomere dysfunction and cellular senescence and dysregulated signaling through the small GTPase, ARF6, in these processes.

Effects of Aging on Arterial Function and Atherosclerosis:

Advancing age is associated with vascular dysfunction and increased risk of cardiovascular diseases such as atherosclerosis, although the underlying mechanisms are incompletely understood. My laboratory seeks to elucidate the role of mTOR, miR-92a and ARF6 in age associated arterial dysfunction and atherosclerosis.

Inhibition of mTOR with rapamycin has been demonstrated to increase lifespan in mice, suggesting that mTOR activation with aging may play a central role in the aging process. My laboratory seeks to elucidate the role of altered mTOR signaling in the vascular aging phenotype and to explore the use of novel interventions that can mimic the beneficial effects of rapamycin.

MicroRNAs (miRs) are small noncoding RNAs that regulate translation of messenger RNA and have important physiological effects, acting on multiple gene targets often related to a specific cellular process/signaling pathway. MiR-92a, a member of the miR-17-92 cluster, is important in vascular growth during development and tumorogenesis and is decreased in advanced age. Our laboratory seeks to determine if an age-associated reduction in microRNA, miR-92a and its cluster miR-17-92, underlies age-associated arterial dysfunction and accelerated atherosclerotic.

Age-associated chronic inflammation is implicated in both arterial dysfunction and atherosclerosis. Activation of the small GTPase, ADP ribosylation factor 6 (ARF6), is associated with inflammatory states, but the impact of aging on arterial ARF6 is not known. Because ARF6 is also known to be sensitive to changes in shear stress, we seek to determine if ARF6 signaling modulates endothelial function, inflammation and mechanotransduction of turbulent / oscillatory shear and contributes to the development of age-related pro-atherosclerotic arterial dysfunction.