Consequences associated with obesity can be miOgated by shiOing adipose Ossue expansion from hypertrophic to
hyperplasOc expansion; the former increases overall size of exisOng adipocytes and correlates with increased
in¿ammaOon, insulin insensiOvity, and ¿brosis, while the la¿er di¿erenOates new adipocytes from resident
preadipocytes through adipogenesis. Remedying the expansion of our adipose Ossue to favor healthier hyperplasOc
expansion is of the upmost importance to combat the obesity epidemic, as western diets high in fat and carbohydrates
have shown to shiO the balance of fat expansion to the more consequenOal hypertrophic expansion. All preadipocytes
have primary cilia, which are criOcal for their di¿erenOaOon into mature adipocytes. These organelles are typically rich in
signaling components, speci¿cally G protein-coupled receptors (GPCRs), though li¿le is known about ciliary protein
composiOon in preadipocytes. Thus far only one receptor has been discovered in the cilium of preadipocytes, and its
acOvaOon increases ciliary cAMP and subsequent adipogenesis. Increases in cellular cAMP are necessary for ex vivo
adipogenesis, but it is unknown what role compartmentalized ciliary cAMP has in adipogenesis, though ciliary cAMP in
other cell types has been shown to have di¿erenOal funcOons than whole cell cAMP. I hypothesize that cAMP in the
cilium is necessary and su¿cient to induce adipogenesis in preadipocytes, and that a suite of ciliary GPCRs acts to
in¿uence this process in a cilia-dependent manner. My ¿rst aim will de¿ne the role of ciliary cAMP in adipogenesis, using
chemogeneOc and optogeneOc tools to control the generaOon or depleOon of ciliary cAMP during adipogenesis to de¿ne
its su¿ciency and necessity in preadipocyte di¿erenOaOon. My second aim will idenOfy GPCRs that localize to
preadipocyte cilia and invesOgate their physiological roles in adipose expansion and prevalence in healthy versus
unhealthy adipose Ossues.
This work will be conducted at the University of Utah under the guidance of my sponsor, Dr. Keren Hilgendorf, and co-
sponsor, Dr. Jeremy Reiter, both of whom specialize in ciliary signaling. My thesis commi¿ee is composed of
interdisciplinary researchers with a range of specialOes all pertaining to di¿erent porOons of this proposal, such adipose
Ossue, signaling metabolites, GPCRs, and primary cilia signaling. Together, these mentors will provide expert guidance in
all facets of this project. In addiOon, this project will be supported by the work of mulOple university core faciliOes,
including those that o¿er services in cellular microscopy, ¿ow cytometry, mass spectrometry, and metabolomics. These
faciliOes o¿er excellent support and training services to facilitate my growth as a researcher. The training plan presented
was developed to ulOmately prepare me for a future in academia as an independent researcher in the ¿eld of ciliary
signaling and cell fate determinaOon. In addiOon to the technical skills this project will provide, it will also further my
development as a mentor and teacher through university-supported training programs and laboratory opportuniOes. Dr.
Hilgendorf has fostered a supporOve research environment that encourages scienO¿c exploraOon and my development
as a researcher. She has demonstrated dedicaOon to my training and catered her mentorship to re¿ect my career goals.