The body must maintain a pH within a narrow range (7.4±0.05) to sustain life. However, many factors such as kidney disease, diabetes, metabolic diseases, and diet can shift this pH outside the acceptable range. To counter these variations, the body employs a variety of regulatory mechanisms. Although musculoskeletal regulation of pH has been previously reported, the mechanisms by which muscles and bones control acid-base balance are unknown.  My lab will focus on elucidating the relationship between the musculoskeletal system and the acid/base balance in the body. I hypothesize that degradation of muscle, bone, and tendon directly regulates pH at the (1) cellular, (2) local, and (3) systemic levels. This understanding will create a foundation of knowledge for developing therapeutic treatments for diseases such as osteoporosis, muscle wasting, and metabolic acidosis.

1.  CELLULAR ACID/BASE BEHAVIORS:

Osteoporosis, which is responsible for 1.5 million fractures every year (Masi et al, 2008), is often caused by an imbalance between bone dissolution and deposition during remodeling. During remodeling, osteoclasts dissolve collagen and carbonated apatite mineral; however, the rates of dissolution and their relationship to composition are unknown. My lab will focus on understanding the regulatory role of bone composition on bone remodeling. Specifically, I am interested in explaining how carbonate content in bone mineral affects dissolution and ion release at the cellular level. My previous work shows that the addition of carbonate significantly decreases the crystal size, crystallinity, and surface energy while increasing solubility (Deymier, 2017). The addition of carbonate to bone mineral therefore has a significant effect on bone mineral properties and dissolution behavior. I aim to build on my expertise in biomimetic apatites to shed-light on the role of carbonate substitution on regulation of pH during remodeling.

2.  LOCAL ACID/BASE BEHAVIORS:

Disuse increases the risk of joint injury and failure (Deymier, 2016). However, the mechanisms that lead to this increased failure risk remain unknown. My lab will focus on elucidating the mechanisms by which disuse affects the structure and mechanics of the musculoskeletal system. Specifically, I will focus on the effects of disuse on the local acid/base balance and how it affects tendon and bone structure-function. During my previous work as a National Space Biomedical Research Institute First Award fellow I showed that unloading via Botox lead to compromised mechanics and modified structures. However, there is little work done examining the local pH of disused muscles where an increase in glycolysis is known to occur [6]. My aims are to build on my expertise in the structural and mechanical outcomes of unloading to examine the relationship between injury, acidity, and disuse.   

3.  SYSTEMIC ACID/BASE BEHAVIORS:

Hyperchloremic Acidosis (HcA) is present in 20-80% of all critically ill (Gunnerson, 2003; Luft, 2001). HcA, which occurs when blood pH drops below 7.35 and leads to a rapid dissolution of bone mineral, which serves to buffer the acid load. Chronic acidosis results in significant bone loss.  Although the link between bone dissolution and acidosis has been established, no one has investigated whether the natural buffering ability of bone could be harnessed to treat individuals with acidosis. My lab will focus on developing techniques to control bone composition to treat HAc without compromising bone mechanics. Specifically, I am interested in prompting osteoclasts to build bone with varying levels of carbonate that can effectively respond to acidity changes. Ideal treatments of HAc would require release of sufficient buffering bicarbonate without significant bone loss. My expertise in murine husbandry and bone mechanics will enable me to develop cell controlled therapies for treating systemic acidosis.

Accepting Lab Rotation Students: Spring 1 and 2 Block 2025

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