1 Luck begins
Much of the success I have had can be attributed to a good share of luck. I came out of high school interest in science – I’m not sure what I liked about it but I just wanted to learn more. I went to Eastern Illinois University (EIU) in a Pre-Professional route majoring in Zoology. I chose EIU because I wanted to swim competitively and not for any academic reason. I knew the Ray Padovan who had coached me in age-group swimming one summer. I lucked out because EIU had a strong biology program that helped me in graduate school and beyond. After my first semester, Padovan told me I would receive a tuition scholarship through the Athletic Department based on my GPA (not for my phenomenal swimming ability). I came out of Eastern with a BS in Zoology that included 5 physiology courses and a minor in Chemistry. Physiology was really what floated my boat but it took me awhile to get back to it. During my MS in ruminant nutrition, at Southern Illinois University (Carbondale, IL) because of a snowstorm, Amtrak Railroad and Interstate 57 were closed. If the snowstorm had not shut everything down, I would never have met my wife, Sari. This was a huge stroke of luck!
After the MS, I went to the University of Illinois for a PhD. After going through two labs (ruminant nutrition and rumen microbiology), I finally got back to my real interest in physiology with Dr. Paul Harrison (PCH). I would not recommend this path for graduate students as it added a couple years to my PhD program. I worked on heat stress physiology in broilers and ended up with 5 publications (; ; ; ; ). However, the nearly 2-year delay was lucky because I ended up doing a post-doc that ultimately led to an NIH grant a couple years later. I interviewed at the University of New Hampshire but (luckily) I was not hired for that position. One thing that I lacked was post-doc experience.
When I put my PhD committee together, the ‘normal’ number of committee members was 5. I added a sixth member, Dr. Ken Holmes, in the Dept. of Veterinary Biosciences (U of I). Dr. Holmes had developed a new method of measuring blood flow in tissue called a thermal pulse decay (TPD) system. I was lucky enough to have been hired into his lab as a post-doc to work on further development and validation of the TPD system (see ). The TPD method could measure time course changes in blood flow (tissue perfusion) at 3 min intervals in 6 areas in a single organ or multiple organs over several hours. Placement of probes in the renal cortex and medulla, enabled us to take repeated measurements in these regions of the kidney – something that had never been done before.
2 Contributions to science
2.1 Getting started
While working in Dr. Holmes’ lab, Dr. Hassan (in an adjacent lab), came in 1 day and mentioned that while working with a chemical that rapidly depletes hepatic glutathione (GSH)1 levels, he noticed that the rat’s ears turned red. He said, “I think there are changes in blood flow happening – you should see if it affects liver blood flow”. We conducted a set of studies on rats that revealed an inverse relationship between hepatic blood flow and tissue GSH. This study eventually led to an NIH grant.
I took a chance and gave my interview seminar for the Dept. Animal Science (University of Arkansas, UA) on the GSH and liver blood flow study in rats (even though the position was for an Environmental Physiologist in poultry). I was hired and started at the UA, Division of Agriculture in July of 1985. That fall, I attended the American Physiology Society (APS) fall meeting (Niagra Falls, CN) and presented a poster on the apparent inverse relationship between GSH and liver blood flow. Two people stopped by my poster that had a huge impact on me. The first one was Dr. Aubrey Taylor who was President of APS who thought the research was interesting and novel and encouraged me to pursue this rigorously. I submitted the GSH-liver blood flow manuscript one more time and got it accepted in Biochemical Pharmacology (). The second person I met was Dr. Bob Wideman (at Pennsylvannia State University) who was interested in the TPD method and how it might be used for studying blood flow mechanisms in the avian kidney. We ended up doing a series of studies a few years later using his one lobe avian kidney model. That was a very good piece of luck for me.
In early 1986, I gave a seminar for the Chemistry Department at UA the liver blood flow and GSH interrelationship. After the seminar, Dr. Collis Geren (Dept. Chair and later the Dean of the Graduate School) offered to help me package an NIH grant which was extremely fortunate because I had not written a grant proposal before – another piece of luck. Dr. Geren was world renown for his fundamental work in spider venom toxicity. Dr. Geren was also one of those people who looks out for the general good of the community and never self-serving. In 1987, the grant was ranked in the top 5% and fully funded by NIEHS. Starting off as an Assistant Professor with a 5 years large federal grant was extremely lucky. I was able to hire a couple of post doc and graduate students without relying on departmental funds.
2.2 Antioxidants, oxidative stress, blood flow and prostaglandins
To our knowledge, the inverse relationship between GSH and hepatic blood in vivo () was the first time this was reported. Subsequently, we later reported that indomethacin, an inhibitor of prostaglandin synthase, attenuated both the increase in celiac blood flow in broilers (Beers et al., 1990) and hepatic blood flow and elevations in 6-keto PGF1a (prostacyclin) in rabbits () and swine (). There were also inverse relationships between GSH levels and prostaglandin synthesis in renal medullary homogenates (). The increased blood flow in tissues following toxic insult could contribute to tissue damage as well as help in tissue repair and recovery.
2.3 Interorgan circulation of glutathione
A fundamental study by described interorgan circulation of GSH that entailed synthesis in the liver followed by export into the general circulation and taken up by extrahepatic tissues. In that study, blood samples were taken at a single time point; ∼20 from a systemic artery and hepatic portal vein (representing afferent sources of blood entering the liver) with only 4 samples obtained from the hepatic vein which is difficult to reach due to its location next to the diaphragm within the thoracic cavity. Birds, however, do not have a diaphragm, thus it was possible to obtain repeated blood samples from the hepatic vein. This was facilitated with a hooked needle that Bob Wideman used in his avian kidney studies. In the study by Wang et al. (1998), interorgan circulation of GSH was clearly confirmed and was documented in the avian liver for the first time. This technique also enabled assessment effects of a stress hormone (norepinephrine) that stimulated GSH release from the liver () and hepatic extraction of circulating amino acids and impact of methionine infusion across the hepatic vasculature ().
2.4 Oxidative stress, mitochondria, and pulmonary hypertension syndrome (PHS)
At the fall physiology meeting in 1986, Bob Wideman mentioned a new problem in the poultry industry that he had seen at altitude and was now showing up at sea level; ascites (PHS). I visited his lab after the meeting and he showed me evidence of lung damage in day old chicks. The GSH-oxidative stress studies associated with the NIEHS studies led to an interest in determining if oxidative stress was associated with PHS and presented in report by Enkvetchakul et al. (1993) and later to a study investigating Vit E and PHS (). This research also sparked an interest in mitochondrial function and biochemistry as mitochondria are a major site of endogenous oxidative stress. Site-specific defects in the electron transport chain that would contribute to higher oxidative stress were identified in liver (), lung (), and heart (Tang et al., 2002) obtained from broilers with PHS.
2.5 Mitochondria and feed efficiency
Interest in mitochondria continued with studies that revealed evidence of a link between muscle mitochondrial function and feed efficiency (FE). In a series of studies, evidence of mitochondrial dysfunction and/or biochemistry, including site-specific defects in electron transport, in tissues obtained from broilers expressing a low FE phenotype were identified in muscle (; ; ), duodenum (; ), liver (), lymphocytes (), and heart muscle (Tinsley et al., 2010). Differences in proton leak kinetics were also determined in muscle mitochondria between high and low FE groups ().
2.6 Global gene expression and feed efficiency
Because mitochondrial ROS initiate signal transduction, we conducted global gene and protein expression analysis to understand the gene and gene product landscape associated with feed efficiency (; ; , ; ). Interesting aspects of the story were that mitochondria in high FE animals appeared to have enriched ribosomal machinery and protein translation compared to muscle from low FE phenotype (). Based on the global expression studies, further insight into fundamental mechanisms revealed that high FE birds exhibited enrichment of intracellular degradation pathways of autophagy and proteosomes (Piekarski-Welsher et al., 2018). This suggests that high FE animals may either repair proteins quicker or turnover damaged proteins to a greater extent than low FE. The myostatin signaling pathway was shown to play a role in the phenotypic expression of FE also (). Using an analytical method of regulatory impact factor (RIF) analysis (; ; ) identified progesterone as having a major influence on the phenotypic expression of FE (). This led to work that clearly identified the presence of several hormone receptors including progesterone on avian mitochondria ().
2.7 Water efficiency
Since 2019, I have been lucky to serve as project director (PD) on a USDA NIFA Sustainable Agriculture Systems project2. The “catalysts” for this were Dr.’s Dridi (UA) and Lei (Cornell University) coerced me into being the PD. One sub-aim on this project was headed up by Dr. Sara Orlowski (UA) who successfully selected broilers for low water conversion ratio (LWCR, water efficient) and high water conversion ratio (HWCR, water inefficient) from a modern random bred (MRB) base broiler population3 (). A series of studies have been conducted to assess the effect that divergent selection has had on gene and/or protein expression in the hypothalamus, kidney, intestines, immune systems, and meat quality (see Aloui et al., 2024; ; ; ; Santamaria et al., 2025). While selection for feed conversion ratio (FCR) has a positive impact on water, selection for WCR has resulted in even further improvements in water use efficiency. These studies hopefully will provide a way to help the poultry industry down the road as water scarcity becomes even more prevalent in the face of hotter temperatures over longer periods of time.
3 Summary
Have I been lucky? Absolutely! Many events have put me in the right place at the right time. I have been fortunate to have had great graduate students, post-docs and collaborators. I was part of the development of a Center that brought in some of the best faculty in poultry science. I also want to acknowledge contributions by Dr. Kentu Lassiter who has been working in the lab since he was an undergraduate student. Finally, I’ve also been extremely lucky to have received funding throughout my career through various Federal agencies, State, and industry sources.
Statements
Author contributions
WB: Writing – original draft.
Funding
The author(s) declared that financial support was received for this work and/or its publication. USDA NIFA SAS 2019-69012-29905. Empowering the US Broiler Industry for Transformation and Sustainability.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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The author(s) declared that generative AI was not used in the creation of this manuscript.
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Correction note
This article has been corrected with minor changes. These changes do not impact the scientific content of the article.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Footnotes
1.^Glutathione is an endogenous antioxidant found at mM levels in most cells. It plays vital roles in numerous redox reactions in the cell.
2.^USDA NIFA SAS 2019-69012-29905. Empowering the US Broiler Industry for Transformation and Sustainability.
3.^The modern random bred (MRB) line was established in 2016 and represented a composite of commercial broiler lines at that time.
References
1
AlouiL.GreeneE. S.TablerT.LassiterK.BottjeW. G.OrlowskiS.et al (2024). Effect of heat stress on hypothalamic expression profile of water homeostasis genes in low‐ and high‐water efficient chicken lines. Phys. Reports12 (5), e15972. 10.14814/phy2.15972
2
AndersonM. E.BridgesR. J.MeisterA. (1980). Direct evidence for interorgan transport of glutathione and that the non-filtration renal mechanism for glutathione utilization involves γ−glutamyl transpeptidase. BBRC96, 848–852. 10.1016/0006-291X(80)91433-3
3
ArkinH.HolmesK. R.ChenM. M.BottjeW. G. (1986). Thermal pulse decay (TPD) method for the simultaneous measurement of local thermal conductivity and blood perfusion: a theoretical analysis. J. Biomech. Eng.108, 204–214. 10.1115/1.3138604
4
BeersK. W.NejadH.BottjeW. G. (1990). Indomethacin attenuates celiac blood flow hyperemia following glutathione depletion. Biochem. Pharm.40, 2331–2335. 10.1016/0006-2952(90)90730-9
5
BottjeW. G.HarrisonP. C. (1985a). The effect of tap water, carbonated water, sodium bicarbonate and calcium chloride on blood acid-base balance in cockerels subjected to heat stress. Poult. Sci.64, 107–113. 10.3382/ps.0640107
6
BottjeW. G.HarrisonP. C. (1985b). Effect of carbonated water on growth of cockerels subjected to constant and cyclic heat stress temperatures. Poult. Sci.64, 1285–1292. 10.3382/ps.0641285
7
BottjeW. G.HarrisonP. C. (1986a). The effect of heat stress and hypercapnia on postprandial intestinal hyperemia in domestic cockerels. Poult. Sci.65, 1607–1614.
8
BottjeW. G.HarrisonP. C. (1986b). Alpha-adrenergic regulation of celiac blood flow and plasma catecholamine response during acute heat stress in fed cockerels. Poult. Sci.65, 1598–1606. 10.3382/ps.0651598
9
BottjeW. G.HarrisonP. C. (1987). Celiac cyclic blood flow pattern response to feeding and heat stress exposure. Poult. Sci.66, 2039–2042. 10.3382/ps.0662039
10
BottjeW. G.EnkvetchakulB.MooreR.McNewR. (1995). Effect of α-tocopherol on antioxidants, peroxidation, and the incidence of pulmonary hypertension syndrome in domestic fowl. Poult. Sci.74, 1356–1369.
11
BottjeW.GlahnR.BeersK.NejadH.GraupnerW.HolmesK. R. (1991). Indomethacin attenuation of hepatic perfusion and plasma 6-keto PGF1α elevations following glutathione depletion in rabbits. Biochim. Biophys. Acta1073, 168–176. 10.1016/0304-4165(91)90198-P
12
BottjeW.GlahnR.BeersK.NejadH.HolmesK. (1992). Effect of diethyl maleate on glutathione, blood pressure, hepatic and renal cortical perfusion and portal 6-ketoPGF1a and TxB2 in swine. Comp. Biochem. Physiol.101C, 125–129. 10.1016/0742-8413(92)90209-P
13
BottjeW.TangZ.IqbalM.CawthonD.OkimotoR.WingT.et al (2002). Association of mitochondrial function with feed efficiency within a single genetic line of Male broilers. Poult. Sci.81, 546–555. 10.1093/ps/81.4.546
14
BottjeW.BrandM. D.Ojano-DirainC.LassiterK.ToyomizuM.WingT. (2009). Mitochondrial proton leak kinetics and relationship with feed efficiency within a single genetic line of Male broilers. Poult. Sci.88, 1683–1693. 10.3382/ps.2009-00100
15
BottjeW. G.KongB.SongJ. J.HargisB. M.LassiterK.WingT.et al (2012). Gene expression in breast muscle associated feed efficiency in a single male broiler line using a chicken 44k microarray II. Differentially expressed focus genes. Poult. Sci.91, 2576–2587. 10.3382/ps.2012-02204
16
BottjeW. G.KongB.ReverterA.WaardenbergA. J.LassiterK.HudsonN. J. (2017a). Progesterone signaling in broiler skeletal muscle is associated with divergent feed efficiency. BMC Syst. Biol.11, 29. 10.1186/s12918-017-0396-2
17
BottjeW. G.LassiterK.Piekarski-WelsherA.DridiS.Gomez-ReverterA.HudsonN. J.et al (2017b). Proteogenomics reveals enriched ribosome assembly and protein translation in Pectoralis major of high feed efficiency pedigree broiler males. Front. Physiology8 (article 306), 1–11. 10.3389/fphys.2017.00306
18
CawthonD.McNewR.BeersK. W.BottjeW. G. (1999). Evidence of mitochondrial dysfunction in broilers with pulmonary hypertension syndrome (Ascites): effect of t-butyl hydroperoxide on function, glutathione and related thiols. Poult. Sci.78, 114–125. 10.1093/ps/78.1.114
19
EnkvetchakulB.BottjeW.AnthonyN.MooreR.HuffW. (1993). Compromised antioxidant status associated with ascites in broilers. Poult. Sci.72, 2272–2280. 10.3382/ps.0722272
20
HiltzJ. Z.OrlowskiS. K.HarringtonL. N.MaynardC. W.TablerT.AnthonyN. B. (2021). Applied research note: development of a novel low flow water monitoring systemin poultry/agriculture systems. J. Appl. Poult. Res.30, 1–6. 10.1016/j.japr.2021.100151
21
HudsonN. J.ReverterA.DalrympleB. P. (2009). A differential wiring analysis of expression data correctly identifies the gene containing the causal mutation. PLoS Comput. Biol.5 (5), e1000382. 10.1371/journal.pcbi.1000382
22
HudsonN. J.DalrympleB. P.ReverterA. (2012). Beyond differential expression: the quest for causal mutations and effector molecules. BMC Genomics13, 356. 10.1186/1471-2164-13-356
23
IqbalM.CawthonD.WidemanR. F.Jr.BottjeW. G. (2001). Lung mitochondrial dysfunction in pulmonary hypertension syndrome. I. Site-specific defects in the electron transport chain. Poult. Sci.80, 485–495. 10.1093/ps/80.4.485
24
KongB.-W.SongJ. J.LeeJ. Y.HargisB. M.WingT.LassiterK.et al (2011). Gene expression in breast muscle associated feed efficiency in a single male broiler line using a chicken 44k microarray. I. Top differentially expressed genes. Poult. Sci.90, 2535–2547. 10.3382/ps.2011-01435
25
KongB.-W.LassiterK.PiekarskiA.Reverter-GomezA.HudsonN. J.BottjeW. G. (2016). Proteomics of breast muscle tissue associated with the phenotypic expression of feed efficiency within a pedigree male broiler line. I. Highlight on mitochondria. PLoS11 (5), e0155679. 10.1371/journal.pone.0155679
26
LassiterK.IqbalM.PumfordN. R.Ojano-DirainC.TinsleyN.WingT.et al (2006). Differential expression of mitochondrial and extra-mitochondrial proteins in lymphocytes of low and high feed efficient male broilers. Poult. Sci.85, 2251–2259. 10.1093/ps/85.12.2251
27
LassiterK.DridiS.GreeneE. S.KongB.BottjeW. G. (2018). Identification of mitochondrial hormone receptors in avian muscle cells. Poult. Sci.97, 2926–2933. 10.3382/ps/pey126
28
LassiterK.AlouiL.GreeneE. S.MaqaedaM.TablerT.DridiS.et al (2024). Water homeostasis gene expressed in the kidneys of broilers divergently selected for water conversion ratio. Poult. Sci.104, 104560. 10.1016/j.psj.2024.104560
29
LassiterK.LoujainA.GreenE. S.MaqaedaM.SchaefferK.RoachB.et al (2025). Intestinal gene expression in heat-stressed broilers selected for high water efficiency. Front. Avian Physiol.
30
NejadH. H.BottjeW. G. (1992). Glutathione depletion and rabbit renal medulla prostacyclin and thromboxane: levels in vivo and following homogenate incubation in vitro. Int. J. Biochem.24, 561–564. 10.1016/0020-711X(92)90327-W
31
Ojano-DirainC.IqbalM.CawthonD.SwongerS.WingT.CooperM.et al (2004). Site-specific effects in electron transport in duodenal mitochondria is associated with low feed efficiency in broiler breeder males. Poult. Sci.83, 1394–1403. 10.1093/ps/83.8.1394
32
Ojano-DirainC.TinsleyN. B.WingT.CooperM.BottjeW. (2007). Membrane potential and hydrogen peroxide production in duodenal mitochondria in broilers chickens (Gallus gallus) with low and high feed efficiency. Comp. Biochem. Physiol.147, 934–941.
33
OrlowskiS.GreeneE. S.LassiterK.TablerT.BottjeW.DridiS. (2024). Research note: carcass yield and meat quality in high-and low-water efficient broiler lines exposed to heat stress. Poult. Sci.103 (9), 103921. 10.1016/j.psj.2024.103921
34
Piekarski-WelsherA.GreeneE.LassiterK.KongB. C.DridiS.BottjeW. (2018). Enrichment of autophagy and proteosome pathways in breast muscle of feed efficient pedigree male broiler. Front. Physiol.26 (9), 1342. 10.3389/fphys.2018.01342
35
ReverterA.HudsonN. J.NagarajS. H.Perez-EncisoM.DalrympleB. P. (2010). Regulatory impact factors: unraveling the transcriptional regulation of complex traits from expression data. Bioinformatics26 (7), 896–904. 10.1093/bioinformatics/btq051
36
SantamariaJ. M.BeckC. N.OrlowskiS. K.MaquedaM.BottjeW. G. (2025). Selection for improved water efficiency in broiler breeder lines does not negatively impact immune response capabilities to Gram- and Gram+ bacterial components and a killed Salmonella enteritidis vaccine. Vet. Sci.12, 279. 10.3390/vetsci12030279
37
SongZ.CawthonD.BeersK.BottjeW. G. (2000). Hepatic and extra-hepatic stimulation of glutathione release by norepinephrine. In Vivo. Poult. Sci.147 (4), 934–941. 10.1016/j.cbpa.2007.02.029
38
SongZ.BeersK.DibnerJ. J.Vázquez-AñónM.McNewR.BottjeW. G. (2001). Hepatic extraction of plasma free amino acids and response to hepatic portal venous infusion of methionine sources in anesthetized SCWL males. Comp. Biochem. Phys. (B)130, 237–250. 10.1016/s1096-4959(01)00430-4
39
TangZ.IqbalM.CawthonD.BottjeW. G. (2002). Heart and muscle mitochondrial dysfunction in pulmonary hypertension syndrome in broilers. Gallus Domest. Comp. Biochem. Physiol.132, 527–540. 10.1016/s1095-6433(02)00005-3
40
TinsleyN.IqbalM.PumfordN. R.LassiterK.Ojano-DirainC.WingT.et al (2010). Investigation of mitochondrial protein expression and oxidation in heart muscle in low and high feed efficient male broilers in a single genetic line. Poult. Sci.89, 349–352. 10.3382/ps.2009-00138
41
WangS.BottjeW. G.CawthonD.EvensonC.BeersK.McNewR. (1998). Hepatic export of glutathione and uptake of constituent amino acids, glutamate and cysteine in broilers in vivo. Poult. Sci.77, 1556–1564. 10.1093/ps/77.10.1556
Summary
Keywords
mitochondria, blood flow, glutathione, oxidative stress, physiology
Citation
Bottje WG (2026) Sometimes it’s good to be lucky: blood flow, glutathione, oxidative stress, and mitochondria. Front. Physiol. 16:1766585. doi: 10.3389/fphys.2025.1766585
Received
12 December 2025
Revised
24 December 2025
Accepted
26 December 2025
Published
09 February 2026
Corrected
10 March 2026
Volume
16 - 2025
Edited by
Sandra G. Velleman, The Ohio State University, United States
Reviewed by
Paul Siegel, Virginia Tech, United States
Updates
Copyright
© 2026 Bottje.
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*Correspondence: Walter Gay Bottje, wbottje@uark.edu
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.