Turning Back The CLOCK: A Look Into The History of Circadian Oscillations

As an early career researcher, I feel that I lack some critical background knowledge of foundational studies and scientists in research. Most of my blog posts will focus on recent papers or topics, and I’ll dig into the history of that topic to find out how we got to where we are.

Many fantastic papers have been published on the circadian clock lately. Drs. David Montaigne and Bart Staels recently published a Viewpoint on the topic of the circadian clock and cardiovascular disease in Circulation Research.1 My basic understanding of the circadian clock is that transcription factors, CLOCK and BMAL1, are critical proteins. Light is sensed at the retina and the optic nerve transmits a signal to the suprachiasmatic nuclei then throughout the body. Since light (historically) came from the sun, these proteins and the clock functions generally oscillate with day and night. Knocking out or mutating clock proteins can alter metabolism, immunity, and a slew of other systems.

A 2013 paper published in Circulation by Xiaoyue Pan and colleagues showed increased atherosclerosis in mice where the CLOCK protein was mutated, thus disrupting the circadian rhythm.2 The mechanisms appeared to be elevated ApoB48 particles and increased macrophage cholesterol scavenging. In 2009, a Circulation paper by Ciprian Anea and colleagues showed increased collagen deposition and fibrotic remodeling after arterial ligation in the carotid artery of BMAL1 knockout mice.3 Finally, a 2018 Cell Metabolism paper by Carla Winter showed that myeloid cells behave in a circadian fashion.4 These are impressive recent papers, but how did we get to this point? I wanted to gain a better understanding of where the science of biological clocks began.

My first stop was the “circadian clock” page on Wikipedia, but it was lacking any historical context.5 Next, I found a review on Pubmed from 1993 by a scientist named Colin Pittendrigh in the Annual Review of Physiology entitled, Temporal organization: reflections of a Darwinian clock-watcher.6 This review was more of an autobiography than review, but it was a joy to read. I would suggest reading the entire review, but I’m going to summarize some it here. After reading a few paragraphs it became evident that Colin Pittendrigh might be a prominent figure in the science of biological clocks. I did a quick search (the Wikipedia page for “Colin Pittendrigh”) and found this in the second sentence, “…father of the biological clock…”, which came from a Stanford press release upon Pittendrigh’s death.7,8

What I found in Pittendrigh’s 1993 “reflections” was that he was an extraordinary scientist, and an interesting man. Pittendrigh begins by recounting how he became interested in biology. Living in the north of England, he kicked a soccer ball through the window of the town hall and needed to replace it. Needing money, he entered a contest for the best wild flower collection from the local Boy Scouts and won. This sparked his biological interest. During high school, Pittendrigh discovered Charles Darwin’s works which greatly influenced him. He says that his Darwinian beliefs later survived exposure to Lamarckian convictions of a college professor. During wartime in the 1940s, he was in Trinidad and was instructed to focus on breeding vegetables for the campaign. Later, he studied Malaria by focusing on habits of mosquitoes, and eventually he studied drosophila behavior. During these experiences, he observed periodicity in the behaviors of these organisms.6

With influences from colleagues, Pittendrigh reasoned that the biological clock must be endogenous.6 During his time at Princeton and Stanford, Pittendrigh published many papers including five in the journal, Science. Almost all of these were published on the circadian oscillations of plants and animals; however, he had other interests, as well. Notably, a 1965 Science paper titled, Proposed Biological Exploration of Mars between 1969 and 1973.9 Pittendrigh’s career in science was monumental, although he didn’t discover the proteins involved in biological clocks. The CLOCK protein was discovered in 1993 and BMAL1 was discovered in 1997, the year after Pittendrigh’s death.10,11 These discoveries undoubtedly wouldn’t have been made without the pioneering work of Colin Pittendrigh.

Dr. Pittendrigh’s life and discoveries are remarkable and in his writing, he constantly references others that were instrumental to his ideas and discoveries. With mounting pressure to have first or last author publications in our time (forgive the pun), it is easy to overlook others who make scientific progress possible. And although Colin Pittendrigh did not study cardiovascular diseases, his findings are having an impact on cardiovascular medicine now. This highlights the interdisciplinary nature of science and how ideas from diverse fields impacts others. It is always beneficial to read papers, attend seminars, and speak with colleagues from diverse fields to broaden our own experimental approaches and ideas.



  1. David Montaigne & Bart Staels. Time to Check the Clock in Cardiovascular Research and Medicine. Circulation Research. 2018; 123:648–650
  2. Xiaoyue Pan, Xian-Cheng Jiang, and M. Mahmood Hussain. Circulation. 2013 Oct 15; 128(16): 1758–1769.
  3. Anea CB, Zhang M, Stepp DW, Simkins GB, Reed G, Fulton DJ, Rudic RD. Circulation. 2009 Mar 24;119(11):1510-7
  4. Winter C, Silvestre-Roig C, Ortega-Gomez A, Lemnitzer P, Poelman H, Schumski A, Winter J, Drechsler M, de Jong R, Immler R, Sperandio M, Hristov M, Zeller T, Nicolaes GAF, Weber C, Viola JR, Hidalgo A, Scheiermann C, Soehnlein O. Cell Metab. 2018 Jul 3;28(1):175-182.e5
  5. https://en.wikipedia.org/wiki/Circadian_clock
  6. S. Pittendrigh. Temporal organization: reflections of a Darwinian clock-watcher. Annu. Rev. Physiol. 55, 17 16-54. 1993.
  7. https://en.wikipedia.org/wiki/Colin_Pittendrigh
  8. Stanford University News Service. https://news.stanford.edu/pr/96/960325pittendrig.html 1996.
  9. Pittendrigh CS. Proposed Biological Exploration of Mars between 1969 and 1973. Science. 1965 Apr 30;148(3670):667.
  10. King DP, Zhao Y, Sangoram AM, Wilsbacher LD, Tanaka M, Antoch MP, Steeves TD, Vitaterna MH, Kornhauser JM, Lowrey PL, Turek FW, Takahashi JS. Positional cloning of the mouse circadian clock gene. Cell. 1997 May 16;89(4):641-53.
  11. Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu YZ, Pray-Grant M, Perdew GH, Bradfield CA (March 1997). “Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway”. The Journal of Biological Chemistry. 272 (13): 8581–93.



Funding the Business of Science: Strategies for Early Career Scientists

During my graduate training, I learned how to write research proposals and manuscript, battle with the IRB, collect and analyze data, present my research in various settings, and handle regular (sometimes daily) rejection like a champ. I received excellent training from mentors who will always be my giants. However, as I have progressed through the early stages of my academic career, I have come to realize there are so many things about being an academic scientist that I never learned in graduate school.

The first thing is that, while science is (sometimes) a noble pursuit of generating new knowledge that will advance the human condition, it is also a business. I’ve never started a business nor have I considered myself entrepreneurial, but I believe in order to have a viable business model, one needs money to turn a great idea into something someone will pay for. It turns out that entrepreneurs and scientists have that common – this is why I was excited to attend the early career session on Sunday morning humorously titled, “WTF: Where’s the Funding?”

Even before we graduate with what we all hope is our terminal degree, we are primed by the academic enterprise to fund our work, and ultimately ourselves. For most of us it’s written into our first contracts. But after the glow of actually having a paying job wears off, we are left to agonize over the question, “How do we break into a system that is seemingly impenetrable to newcomers?” This was the very question this session addressed in an early career panel covering governmental, foundation, and industry-supported funding for early career scientists.

The panel started out acknowledging that the goal of every early stage investigator is R-level NIH funding, with its generous indirects and fabled prestige; however, it can be difficult for most of us to achieve this goal soon after completing our training. Against that backdrop this frank panel discussed how to  navigate two alternative funding sources industry funding and foundation funding. Jarett Barry, MD of UT Southwestern summarized these opportunities as “I think of industry, and even American Heart Association [foundation] funding as a pop off valve– a strategy used to complement traditional funding.” For many of us, a pop off valve is exactly what we need to keep our science going during the early, lean years. Further, these types of funding streams can help establish us as experts in our field and provide data needed to publish good papers and serve as preliminary data in future grants.

However, industry and foundation grants are not without their downsides. The panel agreed with Majken Jensen, PhD of the Harvard T.H. Chan School of Public Health, who said these grants are often smaller than federal grants, tend to favor academic celebrities, have low/no indirect rates and can be more heavily taxed by academic institutions, and (in the case of industry funding) can open us up to potential conflicts of interest. But science is a business and early career scientists need money to do their work, so with the limitations acknowledged the panel started to share strategies for obtaining foundation and industry funding.

  1. Develop a wide network and deftly use it. In addition to academic celebrities, science peers, and mentors, this needs to include industry and grant officials. The panel’s suggestions on how to accomplish this were fundamental: present at meetings and engage with people at the posters; strategically serve on panels and committees; and ask your mentors to introduce you to key people in funding organizations.
  2. Build a team of people at your institution who are supportive of your success. This team can include those academic celebrities who can open new opportunities for you. The committee acknowledged that while it can be intimidating to approach seasoned investigators and seek out their advice and mentorship, you need to do it. They will not come to you. You need to be prepared and persistent when asking for assistance, but it is worth it as having these allies can open amazing new doors.
  3. Write. Potential funders will look at your previous publications when determining whether or not to fund you. You need to have enough of a track record of high quality papers that will give them confidence that you will use their funding to do good science and improve the human condition.

In the end, all panelists had a common theme: if we boldly and strategically pursue all relevant funding opportunities, we can be successful.

This session left me optimistic about the future of not just funding my own research, but much of the incredible research of early career scientists. While securing funding is an exercise in endurance and humility, we don’t have to bang our head against the wall forever. If we learn from each critique, persevere, revise and repackage our ideas, and surround ourselves with an amazing team of our own choosing, eventually we will prevail.



Scientific Sessions 2018 – You Should Be Here!

This year I decided to attend American Heart Association Sessions in Chicago rather than online as I did last year. This meeting was not for the faint at heart. There were sessions for everyone. So much so that people were packed in meeting halls with overflow standing around hoping to get a glimpse of the happenings from the doorway. I, on the other hand, went to #AHA18 armed with a schedule and the determination to follow it strictly. My day started with media meetings to hear about any breaking news and novel findings. After, there were meetings all day covering hypertension, mental disorders, diabetes, and more. The vast amount of science being presented necessitated variety of disorders covered in each session with only an underlying commonality. Even as I went on the floor to experience the trade show, not only were there vendors chatting to the attendees about the products represented by each company, but also sessions ranging from clinical trials to device utilization in patient care.

Being that all the official AHA Early Career Bloggers are members of different AHA Councils, we do not always get the opportunity to meet. This was the first opportunity I have had to meet a large number of my blogging colleagues as well as AHA staff that I correspond via email. Initially walking through the McCormick Center looking for meeting halls, I was overwhelmed. To be able to network with such an impressive crowd sparked apprehensions. Then I remembered I was armed with my schedule and would to follow it without deviation; from meeting key opinion leaders to reconnecting with my network and potentially making more connection. Learning how to navigate though a conference as massive as this through going to Experimental Biology. All those previous sessions allowed me to navigate #AHA18 successfully. I look forward to another productive day of learning and networking here in Chicago.

You should be here!



What to expect at Joint Hypertension 2018 Scientific Sessions – Treating Hypertension in 2018

Two AHA Councils, the Council on HAHA|ASH Hypertension Scientific Sessions 2018ypertension and the Council on Kidney in Cardiovascular Disease, have joined forces with the American Society of Hypertension to make Joint Hyptertension 2018 Scientific Sessions (#Hypertension18) among the most impactful. Dr. Karen Griffin, FAHA Vice Chair for the Council on Hypertension Scientific Sessions Planning Committee calls it the “premier scientific meeting on hypertension in the world”. Understandably so; it boast experts from areas of cardiorenal disease, cardiovascular disease, stroke, and genetics to make for a vast cross-disciplianry session with the up-to-date information on hypertension. This year’s meeting received 439 abstracts in 37 categories, over 125 expert peer reviewers, and more than 20 countries represented.

There will be several interactive sessions that will target the established researcher/clinician, early career, and everything in between. With the addition of the new concurrent session D-Track, Clinical Practice Clinical Science and Primary Care tracks, a dimension will be added for elucidate the research science/clinical practice as it relates to patient care. In light of all the sessions that are available one should not have a problem reaching the milestones set by the program coordinators (infra vide).

To point out a few conference highlights, there will be 24 oral sessions, 3 poster sessions, and travel award talks:

The Excellence Award for Hypertension Research (Saturday, September 8, 2018)

  • R. Clinton Webb, PhD, FAHA presents “A Study of the Innate Immune Response in Hypertension”
  • Paul K. Whelton, MB, MD, MSc, FAHA presents “Clinical Trials and Practice Guidelines: Evidence-Based Progress in Lowering Blood Pressure”

Conference Awards

  • 10 Council on Hypertension New Investigator Travel Awards
  • 10 Council on Kidney in Cardiovascular Disease New Investigator Awards
  • 4 New Investigator Travel Awards
  • 6 Hypertension Early Career Oral Award Finalists
  • 12 AFHRE Travel Award for Patient-Oriented or Clinical Research in Hypertension
  • 1 Clinical Science Investigator Award for Excellence in Translational or Clinical Hypertension Research
  • 3 New Investigator Awards for Japanese Fellows

25 Poster Presenters can potentially win the competition this year! Which has gone up significantly from the previous years.

I am excited to go to Chicago for #Hypertension18 this year. If there is anything you need to enhance your experience during your time at the conference contact the program officials (directions in the program book).

I look forward to meeting you all! If you see me around tweeting, introduce yourself. I love meeting new people and learning new things. After all, that is why we are all going, right? 🙂

#Hypertension18 Conference Learning Objectives:

  1. Discuss changes to the AHA/ACC guidelines for the management of hypertension and their clinical implications.
  2. Describe opportunities to improve blood pressure measurement in the clinical setting to provide more accurate results.
  3. Identify immune and inflammatory mechanisms that contribute to the development of hypertension and hypertension-related end-organ damage and discuss the research and clinical implications.
  4. Educate participants about medical approaches for the management of co-morbid obesity in patients with hypertension.
  5. Describe new and emerging strategies for treating resistant hypertension.
  6. Describe participants on the impact of value-based reimbursement on hypertension management and identify opportunities to improve its management.


Leave a comment or tweet @AnberithaT and @AHAMeetings if you have questions or are interested in something else specifically.

Follow me and @American_Heart @AHA_Research @AHAScience and @HyperAHA on twitter for more #HeartSmart information.

For meeting Tweets follow @AHAMeetings @HyperAHA @AHAScience #JAHAMeetingReports @JAHA_AHA for the latest on#Hypertension18!


Growing My Network at BCVS18

Basic Cardiovascular Science 2018 (BCVS18) Scientific Sessions was held in San Antonio this year. I had no initial intention on attending BCVS18, but there was an email notification urging members to participate in a tweeting competition. A Researcher from University of Tennessee Health Science Center challenged me to participate in the competition to try to win one of the two prizes, which ultimately led to my attending the session to assist with social media coverage of the programs. Although I took part in the tweet storm, I was not in the running for the prize. We thought it best to leave those for another researcher.

As with most meetings, this gave me the opportunity to reconnect with people that I had previously met as well as receive career guidance. This meeting was different for me in the respect that, in addition to diving into the science aspect, I actively sought out vendors from organizations of interest to me as a means of gaining insight into transitioning from academic research to industry. This is often an underexplored opportunity at meetings. As a scientist, I spend most of my time going to scientific sessions and poster sessions, and only visit the vendors that I need to meet with to purchase equipment/products or get information about equipment/products that are currently in use in the lab. BCVS is a smaller meeting with fewer vendors allowing more opportunity to go to sessions, as well as spend time gathering career information. I met with people from three noteworthy organizations.

  1. Kara Keehan, Executive Editor for AJP-Heart and Circulatory Physiology took several moments to share with me ways to interact more openly as an introvert. Often times introverted people are perceived as being standoffish or anti-social, but in reality, may just be uncomfortable in social or unfamiliar settings. Kara shared with me some strategies to mingle in social and professional settings to increase my ability to network. For example, walk up to someone and start talking about the last session or Twitter. Additionally, she gave me some insight into the role of an editor and the requirements.
  2. I have become increasingly more interesting in Medical Science Liaison (MSL) positions. Having the ability to be connected to the science and share the information in a way that will help people life a healthier life has resonated with me on many levels. However, understanding how to translate an academic research background into one that will be appealing to recruiters in the industry has proven to be difficult. George Ruth III, Sale Consultant at Pfizer, gave me ample amount of guidance on creating a resume that will catch the eye of the human resource personnel that will be looking to fill those positions. Searching the career website is not always as clear as one would hope, thus George also gave advice on how to identify positions of an MSL with a pharmaceutical company.
  3. Chandler Dental Center came to BCVS to share information about “Oral Systemic Health Services” for patients struggling with inflammatory diseases such as cardiovascular disease. His booth had information about The Heart Gene and articles to support studies that suggest a link between dental health and vascular health. In our one-on-one dialog, he suggested that 78% of people suffering from myocardial infarctions had bacteria in their thrombus that were specific to the mouth. As a dentist, he can take saliva samples and test for the bacterial strain for early detection and treatment, leading to subsequent offset of CVD symptoms. This conversation reiterated the point that physicians rely on scientist to assist in conducting studies that are otherwise not feasible. Thus, Bryce (dentist) works in concert with Bradley Bale (clinical assistant professor) School of Medicine, Texas Tech Health Sciences Center to conduct the cardio-dental research.

When going to a conference, one should take advantage of the total experience. Do not get caught up in only one portion of the meeting. Yes, the science is important, but networking and looking out for the next career step is equally as important. Was it Darwin that said, “Chance favors a prepared mind?”


Leave a comment or tweet @AnberithaT and @AHAMeetings if you have questions or are interested in a specific topic. Also, follow me and @American_Heart for more #HeartSmart information.


Anberitha Matthews, PhD is a Postdoctoral Fellow at the University of Tennessee Health Science Center in Memphis TN. She is living a dream by researching vascular injury as it pertains to oxidative stress, volunteers with the Mississippi State University Alumni Association, serves as Chapter President and does consulting work with regard to scientific editing.


It’s Electric!

As this crowd knows, cardiovascular disease is the leading cause of death worldwide, and though we’ve made great advancements to reduce morbidity and mortality in these patients, there is a desperate search for innovative new treatment strategies.
Traditionally, most chronic conditions are addressed with small molecule-based drugs that bind to their molecular target, exert downstream effects, and bring about therapeutic benefits. In severe cases, a visit to the operating room may be warranted in addition to a pharmacological treatment. For a heart attack, stenting and timely reperfusion remains the preferred emergency intervention.
Drugs and surgeries, though lifesaving and indispensable, are associated with off-target effects, invasive operations, and other negative complications. The ideal therapy would maximize positive patient outcomes and minimize any associated unpleasantries.
Electroceuticals, also known as bioelectronics, are a radical new approach to medical treatment that harness the power of electricity to safely and precisely treat an array of conditions, from sleep apnea to Parkinson’s disease. These are tiny devices that can be implanted in a patient to survey or modify nerve signaling in her body. The most familiar electroceuticals in clinical practice include defibrillators and pacemakers, but recent advances such as vagus nerve and spinal cord stimulation indicate that there is great potential for this field to be explored, expanded, and refined for cardiovascular disease applications.
A spark of interest is growing in the eyes of several industry leaders, and some have already devoted resources to the development and commercialization of bioelectronics medicines. Galvani Bioelectronics, the daughter company of GlaxoSmithKline and Alphabet’s Verily Life Science, is one such investment in the advancement of electronic medicine.
Basic scientists like me have much curiosity and some concerns. Among them, the neurobiology and molecular mechanisms of how electroceuticals elicit their effects are relatively unexplored in some fields.  Such challenges call on an interdisciplinary community of expert scientists, engineers, and clinicians to focus their talents and push for solutions. Hopefully we will all be shocked (in a good way!) by the disruptive technologies this field will bring us in the future.

You can read further about Electroceuticals Spark Interest here.

Annie Roessler Headshot

Annie Roessler is a PhD Candidate at Loyola University in Chicago, IL. Her research focuses on the neurobiology and molecular mechanisms of electrically-induced cardioprotection. She tweets @ThePilotStudy and blogs at flaskhalffull.com