Jacob Noeker

Pronouns: he/him

Member of MSTP (MD/PhD) program

E-MAIL:  [email protected]

Undergraduate Institution and Major:

The College of Idaho, B.S. in Biology & Psychology, 2018

Graduate Advisor

Alfonso Araque, Department of Neuroscience

Graduate Research:

Exploring the role of cellular level neuromodulation through serotonin induced astrocyte activation. Investigating the role of astrocytes in psychedelic signaling.

Graduate Publications

• Kean, C. M., Tracy, C. J., Mitra, A., Rahat, B., Van Winkle, M. T., Gebert, C. M., Noeker, J. A., Calof, A. L., Lander, A. D., Kassis, J. A., & Pfeifer, K. (2022). Decreasing Wapl dosage partially corrects embryonic growth and brain transcriptome phenotypes in Nipbl+/− embryos. Science Advances, 8(48), eadd4136. doi: https://doi.org/10.1126/sciadv.add4136 
• Park, K.-S., Rahat, B., Lee, H. C., Yu, Z.-X., Noeker, J.A., Mitra, A., Kean, C. M., Knutsen, R. H., Springer, D., Gebert, C. M., Kozel, B. A., & Pfeifer, K. (2021). Cardiac pathologies in mouse loss of imprinting models are due to misexpression of H19 long noncoding RNA. ELife, 10. doi: 10.7554/elife.67250 
• Otero C.E., Noeker J.A., Brown M.M., Wavreil F.D.M., Harvey W.A., Mitchell K.A., Heggland S.J. (2019). Electronic cigarette liquid exposure induces flavor-dependent osteotoxicity and increases expression of a key bone marker, collagen type I. Journal of Applied Toxicology 39(2): 1-11. doi: 10.1002/jat.3777 
• Ha T.T., Burwell S.T., Goodwin M.L., Noeker J.A., Heggland S.J. (2016). Pleiotropic roles of Ca+2/calmodulin-dependent pathways in regulating cadmium-induced toxicity in human osteoblast-like cell lines. Toxicology Letters 260: 18-27. doi: 10.1016/j.toxlet.2016.08.020

Graduate Presentations

Renal Afferent Input to Central Autonomic Blood Pressure Centers. Graduate Program in Neuroscience Colloquium Series, November 2024.

Graduate Awards/Honors

NRSA Fellow on T32 training grant T32-NS105604 2023 
COGS Research Grant 2023

Thesis Committee

Paulo Kofuji, Ph.D., Department of Neuroscience (Chair) 
Alfonso Araque, Ph.D., Department of Neuroscience (Advisor)
Patrick Rothwell, Ph.D., Department of Neuroscience
Sade Spencer, Ph.D., Department of Pharmacology
Alexander Herman, M.D./P.h.D., Department of Neuroscience

Rotations

Marija Cvetanovic, P.h.D., Department of Neuroscience
Patrick Rothwell, P.h.D., Department of Neuroscience 
Alfonso Araque, P.h.D, Department of Neuroscience

Undergraduate Research

Undergraduate work: Electronic cigarettes (e‐cigarettes) are nicotine delivery devices advertised as a healthier alternative to conventional tobacco products, but their rapid rise in popularity outpaces research on potential health consequences. As conventional tobacco use is a risk factor for osteoporosis, we examined whether exposure to electronic liquid (e‐liquid) used in e‐cigarettes affects a bone‐forming osteoblast cell line. My objective was to optimize a cell viability assay using electronic liquids. I developed multiple methods that we standardized and used in the laboratory. I found appropriate concentrations of these unvaped liquids to apply to our cells as a treatment, in addition to standardizing a general protocol to use in the lab for this project. Ultimately, I saw a dose-dependent response to these e-liquid treatments. We partnered with Dr. Ken Cornell at Boise State University to run gas chromatography-mass spectrometry on our e-liquid samples before and after they were vaped, showing a change in chemical composition and multiple new chemicals being generated in the vaped liquids. Next, I showed there were conclusive effects on alkaline phosphatase (ALP) activity, suggesting that osteotoxicity was not targeting cell differentiation or mineralization mechanisms. I found a consistent dose-dependent response that was not altered by the presence of nicotine and concluded that the flavoring agents in these e-liquids were contributing to the different levels of osteotoxicity. We generated a toxicity gradient of flavors that was consistent between two human osteoblast-like cell lines. I conducted immunofluorescence assays to examine a potential effect on collagen, and we saw that e-liquid treatments caused the downregulation of collagen type I mRNA in our cell line. This work was vital because it implicated electronic cigarette liquids as detrimental to bone health. 

Post-baccalaureate: H19 regulates endothelial to mesenchymal transition leading to heart failure: The fundamental focus of Dr. Karl Pfeifer’s lab at NICHD is an imprinted gene cluster—the IGF2/H19 locus. Misexpression of H19 is one cause of Beckwith-Wiedemann Syndrome (BWS)—a developmental disorder characterized by hemihyperplasia. My project focused on the cardiac anomalies that arise in a portion of this patient population. To better understand the molecular and cellular mechanisms for cardiovascular defects, we phenocopied the cardiac anomalies in our BWS model mice by knocking out the imprinting control region of H19. Immediately after joining the lab, I began working with newly generated echocardiography data from a collaborator in the NHLBI. I observed two distinct mutant phenotypes in the 12-month-old mice: one with large hearts and increased wall thickness, and another with abnormal cardiac vasculature. I worked with Dr. Beth Kozel’s lab to investigate vascular anomalies by generating vascular compliance data that confirmed a strong and unusual vascular phenotype in the mutant mice. Previous data generated in the lab showed that H19 lncRNA was localized exclusively to endothelial cells after the early stages of development, so they became our target for investigation. I isolated endothelial cells, from which I collected RNA and performed RNA sequencing. My sequencing data told a compelling story of mutant cells upregulating mesenchymal markers, extracellular matrix proteins, and TGF-beta binding proteins—suggesting that the underlying issue was that our mutants were undergoing a high rate of endothelial to mesenchymal transition (EndMT). We investigated the interaction of H19 with TGF-beta, the primary control pathway for EndMT. The EndMT was prevalent in the H19 knockout model, which was likely contributing to the cardiovascular phenotype and early heart failure. I generated a cell culture system with primary endothelial cells to investigate the EndMT pathology we discovered. The main finding of these studies showed that loss of H19 leads to EndMT, thus causing long-term heart pathologies and heart failure.

Undergraduate Publications

• Kean CM, Tracy CJ, Mitra A, Rahat B, Van Winkle MT, Gebert CM, Noeker JA, Calof AL, Lander AD, Kassis JA, Pfeifer K. Decreasing Wapl dosage partially corrects embryonic growth and brain transcriptome phenotypes in Nipbl(+/-) embryos. Sci Adv. 2022 Dec 2;8(48):eadd4136. doi: 10.1126/sciadv.add4136. Epub 2022 Nov 30. PubMed PMID: 36449618; PubMed Central PMCID: PMC9710879. 
• Park KS, Rahat B, Lee HC, Yu ZX, Noeker J, Mitra A, Kean CM, Knutsen RH, Springer D, Gebert CM, Kozel BA, Pfeifer K. Cardiac pathologies in mouse loss of imprinting models are due to misexpression of H19 long noncoding RNA. Elife. 2021 Aug 17;10. doi: 10.7554/eLife.67250. PubMed PMID: 34402430; PubMed Central PMCID: PMC8425947. 
• Otero CE, Noeker JA, Brown MM, Wavreil FDM, Harvey WA, Mitchell KA, Heggland SJ. Electronic cigarette liquid exposure induces flavor-dependent osteotoxicity and increases expression of a key bone marker, collagen type I. J Appl Toxicol. 2019 Jun;39(6):888-898. doi: 10.1002/jat.3777. Epub 2019 Jan 28. PubMed PMID: 30690755; PubMed Central PMCID: PMC6531321. 
• Ha TT, Burwell ST, Goodwin ML, Noeker JA, Heggland SJ. Pleiotropic roles of Ca(+2)/calmodulin-dependent pathways in regulating cadmium-induced toxicity in human osteoblast-like cell lines. Toxicol Lett. 2016 Oct 17;260:18-27. doi: 10.1016/j.toxlet.2016.08.020. Epub 2016 Aug 21. PubMed PMID: 27558804; PubMed Central PMCID: PMC5671922.

Undergraduate Awards/Honors

Outstanding Poster Presentation- NIH Postbac Poster Day 2019 Recognition for MORE C of I Extracurricular Involvement 2018 
Pfizer Pharmaceuticals Society of Toxicology Undergraduate Travel Award 2018 
Outstanding Biology Student for College Career, College of Idaho 2018
Scarab Award (3.9 + GPA with senior status), College of Idaho 2017 + 2018 
William Sype Pre-Health Scholarship, College of Idaho 2017 – 2018 
IDeA Networks of Biomedical Research Excellence (INBRE) Fellowship 2016 
IDeA Networks of Biomedical Research Excellence (INBRE) Fellowship 2015 
Dean’s List (8x), College of Idaho 2014 – 2018 
Gipson Fellow Scholar, College of Idaho 2014 – 2018 
Whittenberger Fellow, College of Idaho 2014 – 2018
Gipson Presidential Scholar, College of Idaho 2014 – 2018