James Haughian

Postdoctoral Fellowship, University of Colorado, Anschutz Medical Campus, 2012.
Area of Study: Oncology

PhD, University of Colorado, 2008.
Area of Study: Cell and Developmental Biology

MS, University of Wisconsin-Madison, 2002.
Area of Study: Endocrinology and Reproductive Physiology

BS, University of Wisconsin-Madison, 2000.
Area of Study: Dairy Science

High School, Rice Lake High School, 1996.

Instructor, University of Northern-Colorado
School of Biological Sciences (2012-present)

Postdoctoral Research Associate, University of Colorado, Anschutz Medical Campus
Oncology- Breast Cancer (2008-2012)

Cannabidiol and Focus Study (CBD-Focus)

Cannabidiol (CBD), a non-psychoactive hemp derivative, is an attractive therapeutic target, and is most supported by the scientific community as an antiepileptic, anxiolytic, and antipsychotic. Additionally, CBD may cause alterations in aspects of health and fitness, fatigue, stress, calmness, quality of life, cognitive function, ability to maintain focus, sleep quantity, and sleep quality. Cannabidiol may be associated with alterations in inflammatory response in the human body, which has implications in both healthy and diseased populations. In humans, natural killer cells (NKC) contain the highest concentrations of receptors associated with the endocannabinoid system and CBD. Human models have demonstrated that CBD use increases the percentage of NKC in peripheral blood. However, similar models found that CBD administration inhibits markers of NKC cytotoxic function, a beneficial cellular mechanism used to prevent malignant cell transformation and viral infection. The overarching goal of this investigation is to determine the effects of an 8-week CBD intervention on measures of fatigue, stress, calmness, quality of life, cognitive function, focus, health and fitness, and sleep quantity, and sleep quality. In addition, this study will explore a potential CBD mechanism of action with a focus on biomarkers of neural health, inflammation, liver health, kidney health, as well as NKC number and function.

Effects of physical activity on the immune system in preclinical cancer models and cancer patients

Immunotherapies are quickly becoming one the main ‘pillars’ of cancer treatment, yet there is limited data on how physical activity (exercise) could help or hinder cancer patients’ clinical responses to these immune-based therapies. We envision exercise as a low-cost, low-risk, potentially high-impact approach to leveraging the power of a patient’s immune system in the fight against their tumor. Much of our initial work has focused on investigating exercise’s impact on a population of immunosuppressive immune cells called Myeloid-Derived Suppressor Cells (MDSCs) in preclinical animal tumor models. Some of our early results were sufficiently promising to prompt an additional, ongoing study of MDSC populations in human cancer patients undergoing adjuvant exercise therapy at the University of Northern Colorado Cancer Rehabilitation Institute (UNCCRI).

Efficacy of the Flipped Classroom Model in the undergraduate biology classroom

While my teaching style relies heavily on informal experimentation in the classroom, I have pursued more formal research questions in this venue. In collaboration with two educational researchers, Dr. Lacy Cleveland and Dr. Jeffery Olympo (both former UNC postdocs who have since left the University) we investigated the effects of a flipped classroom design and active learning assignments in my non-majors undergraduate biology class. I have presented a poster of the results of this work at the Higher Education Flipped Learning Conference; and despite new geographical challenges, Jeff, Lacy and I have continued work on a research article entitled: “Non-Majors Biology Laboratories: Failed Traditional Approaches Suggest It’s Time for Inquiry-Based Reforms”, that will hopefully find a home in an educational research journal. Since this work is more peripheral to my core research interests, I have not included a draft of this manuscript in Section 4.

Influence of fish oil on corpus luteum function

Early pregnancy failures continue to be a major problem in the beef and dairy industries resulting in millions of dollars lost in meat and milk production. The most significant window of pregnancy loss occurs around day 14 – 18 after mating when slow developing embryos fail to prevent onset of the next estrous cycle. Immature embryos are unable to robustly communicate their presence, and thus prostaglandin F2a escapes the pregnant uterus and destroys the corpus luteum (luteolysis) and its essential progesterone support to the nascent pregnancy. Data suggests supplementing dietary omega-3 fatty acids from fish oil extends the pregnancy recognition window by de-sensitizing the corpus luteum to uterine prostaglandin F2a, but the underlying mechanisms are still largely unknown. A mature corpus luteum exposed to prostaglandin F2a experiences a rapid (within 1 hour) reduction in blood flow and diminished progesterone production due to downregulation of critical progesterone synthesis genes. It is hypothesized that dietary omega-3 fatty acids from fish oil will prevent prostaglandin F2a-induced reductions in luteal blood flow and progesterone production. The objectives of the current study will be to deliver a natural dose of prostaglandin F2a to cattle synchronized to day 14-18 of the estrous cycle and determine whether dietary omega-3 fatty acids preserve luteal: 1) blood flow, 2) progesterone production, and 3) abundance of key progesterone synthesis proteins. It is anticipated that dietary omega-3 fatty acids from fish oil will reduce sensitivity of the corpus luteum to a natural prostaglandin F2a challenge, preserving luteal blood flow and sustaining progesterone secretion. Outcomes from these studies would suggest that the reproductive efficiency of cattle operations could be improved through development of novel, cost-effective omega-3 fatty acid supplementation strategies that reduce luteal prostaglandin F2a sensitivity and maintain progesterone support for the embryo during the critical window that a pregnancy is trying to establish.

Signaling pathways promoting transition from ER-positive luminal to ER-negative basal-like breast cancer

Virtually all of this work was completed early in the evaluation period by myself and a constant flow of undergraduate student researchers working in the lab. Our initial work identified the zinc-finger transcription factor Bcl11a as a potential candidate in the interplay between these breast cancer subtypes. This work has provided many training opportunities for our UNC undergraduates. One of these poster presentations was awarded first place in the Research Excellence Award competition for UNC’s College of Natural and Health Sciences, and was later presented at a national meeting for the McNair Scholars Program. Another group of students presented a research poster on this topic to the 2017 National Conference on Undergraduate Research.

Tumor-secreted factors promoting Myeloid-derived suppressor cell (MDSC) expansion

This work is being done in collaboration with fellow faculty member Dr. Nick Pullen and our new graduate student Viva Rase. Our preliminary data indicate a very robust increase in splenic and circulating MDSCs in BALB/c mice bearing tumors grown from the 4T-1 mammary carcinoma cell line (see Figures 2A and 2B in Garritson manuscript under Section 4). Since MDSCs are formed in the bone marrow, our question is- how do 4T-1 tumors communicate systemically to the bone marrow to expand these immunosuppressive cells? Dr. Pullen included me as co-PI on an external grant written to support this work- unfortunately this initial proposal was not successful (see unfunded Bayer Grant in Section 3). ¬¬¬My present role in this work has been generating CRISPR-mediated knock-outs of target genes we believe are important in tumor-dependent MDSC expansion. Hopefully with additional preliminary data in hand we will be successful in obtaining external funding to support this project.

Areas of Interest

I’ve worked extensively in the biomedical research setting and have identified cellular pathways, for ex. Notch pathway, that explain tumor heterogeneity in breast cancers. We have continued this work using CRISPR genome editing tools to identify additional regulators of the distinct cell phenotypes observed in women’s breast cancers.

Another vein of research that my lab has recently been involved with is the effects of physical activity (exercise) on tumor biology. We are working with members of the University of Northern Colorado Cancer Rehabilitation Institute to develop better prescriptive exercise regimes that will maximize the potential of the human body to slow the growth and progression of existing cancers.

I also enjoy teaching others about the biological world in general, and have brought my love of science into the classroom. I continue to experiment with and document the effects of different styles of active learning in my Biology classes, such as the ‘flipped classroom’ approach.

• Ogba N, Manning NG, Bliesner BS, Ambler S, Haughian JM, Pinto MP, Jedlicka P, Joensuu K, Heikkilä P, Horwitz KB. Luminal breast cancer metastases and tumor arousal from dormancy are promoted by direct actions of estradiol and progesterone on the malignant cells. Breast Cancer Res. 2014 Dec 5;16(6):489.
• Knox AJ, Scaling AL, Pinto MP, Bliesner BS, Haughian JM, Abdel-Hafiz HA, Horwitz KB. Modeling luminal breast cancer heterogeneity: combination therapy to suppress a hormone receptor-negative, cytokeratin 5-positive subpopulation in luminal disease. Breast Cancer Res. 2014 Aug 13;16(4):418.
• Haughian JM, Ginther OJ, Diaz FJ, Wiltbank MC. Gonadotropin-releasing hormone, estradiol, and inhibin regulation of follicle-stimulating hormone and luteinizing hormone surges: implications for follicle emergence and selection in heifers.Biol Reprod. 2013 Jun 27;88(6):165.
• Haughian JM, Pinto MP, Harrell JC, Bliesner BS, Joensuu KM, Dye WW, Sartorius CA, Tan AC, Heikkilä P, Perou CM, Horwitz KB. Maintenance of hormone responsiveness in luminal breast cancers by suppression of Notch. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):2742-7.
• Luo W, Gumen A, Haughian JM, Wiltbank MC. The Role of Luteinizing Hormone in Regulating Gene Expression During Selection of a Dominant Follicle in Cattle. Biol Reprod. 2011 Feb;84(2):369-78.
• Kabos P, Haughian JM, Wang X, Dye WW, Finlayson C, Elias A, Horwitz KB, Sartorius CA. Cytokeratin 5 positive cells represent a steroid receptor negative and therapy resistant subpopulation in luminal breast cancers. Breast Cancer Res Treat. 2010 Jul 28.
• Reno EM, Haughian JM, Jackson TA, Thorne AM, Bradford AP. c-Jun N-terminal kinase regulates apoptosis in endometrial cancer cells. Apoptosis. 2009 Jun;14(6):809-20.
• Haughian JM, Reno EM, Thorne AM, Bradford AP. Protein kinase C alpha-dependent signaling mediates endometrial cancer cell growth and tumorigenesis. Int J Cancer. 2009 Dec 1;125(11):2556-64.
• Haughian JM, Bradford AP. Protein kinase C alpha (PKCalpha) regulates growth and invasion of endometrial cancer cells. J Cell Physiol. 2009 Jul;220(1):112-8.
• Reno EM, Haughian JM, Jackson TJ, Dimitrova IK, Bradford AP. Analysis of Protein Kinase C delta (PKCd) Expression in Endometrial Tumors. Human Pathology. 2008 Jan;39(1):21-9.
• Haughian JM, Jackson TA, Koterwas DM, Bradford AP. Endometrial cancer cell survival and apoptosis is regulated by protein kinase C alpha and delta. Endocr Relat Cancer. 2006. Dec; 13(4):1251-67.
• Sartori R, Haughian JM, Shaver RD, Rosa GJ, Wiltbank MC. Comparison of ovarian function and circulating steroids in estrous cycles of Holstein heifers and lactating cows. J Dairy Sci. 2004 Apr;87(4):905-920.
• Haughian JM, Ginther OJ, Kot K, Wiltbank MC. Relationships between FSH patterns and follicular dynamics and the temporal associations among hormones in natural and GnRH-induced gonadotropin surges in heifers. Reproduction. 2004 Jan;127(1):23-33.
• Navratil AM, Bliss SP, Berghorn KA, Haughian JM, Farmerie TA, Graham JK, Clay CM, Roberson MS. Constitutive localization of the gonadotropin-releasing hormone (GnRH) receptor to low density membrane microdomains is necessary for GnRH signaling to ERK. J Biol Chem. 2003 Aug 22;278(34):31593-602.
• Haughian JM, Sartori R, Gumen A, Guenther JN, Wiltbank MC. Extending the postpartum anovulatory period in dairy cattle with estradiol cypionate. J Dairy Sci. 2002 Dec;85(12):3238-49.