A. John MacLennan

A. John John MacLennan

Associate Professor

Medical Sciences Building

4200

COM Physiology MacLennan Lab - 0576

Medical Sciences Building
Room 4200
Cincinnati, Ohio 45267-0576

Professional Summary

Neurodevelopment and neuroregeneration research

Education

BSc, University of British Columbia 1979 (Biopsychology)

MA, University of Colorado 1983 (Experimental Psychology - Neuropharmacology)

PhD, University of British Columbia 1986 (Neuroscience)

Postdoctoral Fellow, University of California, Los Angeles 1989 (Molecular Biology)

Research and Practice Interests

Research Support

Grant: #R01 National Institutes of Health CNTF Receptors: Neuromuscular Protection and Repair In Vivo Role:PI no cost extension Active Type:Grant

Grant: #R01 National Institutes of Health Endogenous CNTF receptors and adult, in vivo neurogenesis Role:PI 225,000 Active Type:Grant

Grant: #1 R01 NS052700-01A1 Investigators:MacLennan, A John 09-10-2006 -04-30-2011 National Institute of Neurological Disorders and Stroke CNTF Receptors: Neuromuscular Protection/Repair Invivo Role:PI $1,351,452.00 Closed Level:Federal

Grant: #4-R01-NS-35224-07-A0-S0-E1 Investigators:MacLennan, A John 12-01-2000 -05-31-2003 National Institute of Neurological Disorders and Stroke CNFT Receptor Regulation and Function Role:PI $329,879.00 Closed Level:Federal

Grant: #5-R01-NS-39127-05-A0-S0-E0 Investigators:MacLennan, A John 12-01-2000 -06-30-2004 National Institute of Neurological Disorders and Stroke CNFT Receptors and Neuroprotection After Brain Trauma Role:PI $646,222.00 Closed Level:Federal

Grant: #R01 NS066051 Investigators:MacLennan, A John 07-01-2009 -06-30-2014 National Institute of Neurological Disorders and Stroke Endogenous CNTF Receptors and Adult, in Vivo Neurogenesis Role:PI $1,703,227.00 Active Level:Federal

Grant: #Starr Family Spark Grant Investigators:MacLennan, A. 02-17-2017 -02-16-2018 Mayfield Education & Research Fund Novel ALS Treatments Targeting Muscle Ciliary Neurotrophic Factor Receptor Signaling Role:PI $50,000.00 Active Level:Private Non-Profit

Grant: #R01NS113917-01 Investigators:MacLennan, A. 09-15-2019 -06-30-2024 National Institute of Neurological Disorders and Stroke Gene Therapy Targeting of CNTFRalpha and CLC in Muscle to Treat ALS Role:PI $424,160.00 Awarded Level:Federal

Publications

Peer Reviewed Publications

Lee, Nancy; Rydyznski, Carolyn E; Spearry, Rachel P; Robitz, Rachel; Maclennan, A John (2013. )The contribution of ciliary neurotrophic factor receptors to adult motor neuron survival in vivo is specific to insult type and distinct from that for embryonic motor neurons.The Journal of comparative neurology, ,521 (14 ),3217-25

Lee, Nancy; Spearry, Rachel P; Leahy, Kendra M; Robitz, Rachel; Trinh, Dennis S; Mason, Carter O; Zurbrugg, Rebekah J; Batt, Myra K; Paul, Richard J; Maclennan, A John (2013. )Muscle ciliary neurotrophic factor receptor ? promotes axonal regeneration and functional recovery following peripheral nerve lesion.The Journal of comparative neurology, ,521 (13 ),2947-65

Lee, Nancy; Batt, Myra K; Cronier, Brigitte A; Jackson, Michele C; Bruno Garza, Jennifer L; Trinh, Dennis S; Mason, Carter O; Spearry, Rachel P; Bhattacharya, Shayon; Robitz, Rachel; Nakafuku, Masato; MacLennan, A John (2013. )Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis.The Journal of neuroscience : the official journal of the Society for Neuroscience, ,33 (3 ),1241-58

Stefater, M A; MacLennan, A J; Lee, N; Patterson, C M; Haller, A; Sorrell, J; Myers, M; Woods, S C; Seeley, R J (2012. )The anorectic effect of CNTF does not require action in leptin-responsive neurons.Endocrinology, ,153 (6 ),2647-54

Cattoretti, Giorgio; Mandelbaum, Jonathan; Lee, Nancy; Chaves, Alicia H; Mahler, Ashley M; Chadburn, Amy; Dalla-Favera, Riccardo; Pasqualucci, Laura; MacLennan, A John (2009. )Targeted disruption of the S1P2 sphingosine 1-phosphate receptor gene leads to diffuse large B-cell lymphoma formation.Cancer research, ,69 (22 ),8686-92

Lee, Nancy; Robitz, Rachel; Zurbrugg, Rebekah J; Karpman, Adam M; Mahler, Ashley M; Cronier, Samantha A; Vesey, Rachel; Spearry, Rachel P; Zolotukhin, Sergei; Maclennan, A John (2008. )Conditional, genetic disruption of ciliary neurotrophic factor receptors reveals a role in adult motor neuron survival.The European journal of neuroscience, ,27 (11 ),2830-7

Lorenz, John N; Arend, Lois J; Robitz, Rachel; Paul, Richard J; MacLennan, A John (2007. )Vascular dysfunction in S1P2 sphingosine 1-phosphate receptor knockout mice.American journal of physiology. Regulatory, integrative and comparative physiology, ,292 (1 ),R440-6

Miotke, Jill A; MacLennan, A John; Meyer, Ronald L (2007. )Immunohistochemical localization of CNTFRalpha in adult mouse retina and optic nerve following intraorbital nerve crush: evidence for the axonal loss of a trophic factor receptor after injury.The Journal of comparative neurology, ,500 (2 ),384-400

MacLennan, A John; Benner, Shannon J; Andringa, Anastasia; Chaves, Alicia H; Rosing, Joanna L; Vesey, Rachel; Karpman, Adam M; Cronier, Samantha A; Lee, Nancy; Erway, Larry C; Miller, Marian L (2006. )The S1P2 sphingosine 1-phosphate receptor is essential for auditory and vestibular function.Hearing research, ,220 (1-2 ),38-48

Lee, Nancy; Neitzel, Karen L; Di Marco, Annalise; Laufer, Ralph; MacLennan, A John (2005. )Penetrating brain injury leads to activation of ciliary neurotrophic factor receptors.Neuroscience letters, ,374 (3 ),161-5

Lee, Nancy; Neitzel, Karen L; Devlin, Brenda K; MacLennan, A John (2004. )STAT3 phosphorylation in injured axons before sensory and motor neuron nuclei: potential role for STAT3 as a retrograde signaling transcription factor.The Journal of comparative neurology, ,474 (4 ),535-45

MacLennan, A J; Carney, P R; Zhu, W J; Chaves, A H; Garcia, J; Grimes, J R; Anderson, K J; Roper, S N; Lee, N (2001. )An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability. The European journal of neuroscience, ,14 (2 ),203-9

Aberg, M A; Ryttsén, F; Hellgren, G; Lindell, K; Rosengren, L E; MacLennan, A J; Carlsson, B; Orwar, O; Eriksson, P S (2001. )Selective introduction of antisense oligonucleotides into single adult CNS progenitor cells using electroporation demonstrates the requirement of STAT3 activation for CNTF-induced gliogenesis.Molecular and cellular neurosciences, ,17 (3 ),426-43

Varela, C R; Bengston, L; Xu, J; MacLennan, A J; Forger, N G (2000. )Additive effects of ciliary neurotrophic factor and testosterone on motoneuron survival; differential effects on motoneuron size and muscle morphology.Experimental neurology, ,165 (2 ),384-93

MacLennan, A J; Devlin, B K; Marks, L; Gaskin, A A; Neitzel, K L; Lee, N (2000. )Antisense studies in PC12 cells suggest a role for H218, a sphingosine 1-phosphate receptor, in growth-factor-induced cell-cell interaction and neurite outgrowth. Developmental neuroscience, ,22 (4 ),283-95

MacLennan, A J; Neitzel, K L; Devlin, B K; Garcia, J; Hauptman, G A; Gloaguen, I; Di Marco, A; Laufer, R; Lee, N (2000. )In vivo localization and characterization of functional ciliary neurotrophic factor receptors which utilize JAK-STAT signaling. Neuroscience, ,99 (4 ),761-72

MacLennan, A J; Orringer, M B; Beer, D G (1999. )Identification of intestinal-type Barrett's metaplasia by using the intestine-specific protein villin and esophageal brush cytology. Molecular carcinogenesis, ,24 (2 ),137-43

MacLennan, A J; Devlin, B K; Neitzel, K L; McLaurin, D L; Anderson, K J; Lee, N (1999. )Regulation of ciliary neurotrophic factor receptor alpha in sciatic motor neurons following axotomy. Neuroscience, ,91 (4 ),1401-13

Forger, N G; Wagner, C K; Contois, M; Bengston, L; MacLennan, A J (1998. )Ciliary neurotrophic factor receptor alpha in spinal motoneurons is regulated by gonadal hormones. The Journal of neuroscience : the official journal of the Society for Neuroscience, ,18 (21 ),8720-9

Chalazonitis, A; Rothman, T P; Chen, J; Vinson, E N; MacLennan, A J; Gershon, M D (1998. )Promotion of the development of enteric neurons and glia by neuropoietic cytokines: interactions with neurotrophin-3. Developmental biology, ,198 (2 ),343-65

Li, Y; MacLennan, A J; Rogers, M B (1998. )A putative G-protein-coupled receptor, H218, is down-regulated during the retinoic acid-induced differentiation of F9 embryonal carcinoma cells.Experimental cell research, ,239 (2 ),320-5

MacLennan, A J; McLaurin, D L; Marks, L; Vinson, E N; Pfeifer, M; Szulc, S V; Heaton, M B; Lee, N (1997. )Immunohistochemical localization of netrin-1 in the embryonic chick nervous system. The Journal of neuroscience : the official journal of the Society for Neuroscience, ,17 (14 ),5466-79

Maclennan, A J; Marks, L; Gaskin, A A; Lee, N (1997. )Embryonic expression pattern of H218, a G-protein coupled receptor homolog, suggests roles in early mammalian nervous system development. Neuroscience, ,79 (1 ),217-24

Kordower, J H; Yaping-Chu, ; Maclennan, A J (1997. )Ciliary neurotrophic factor receptor alpha-immunoreactivity in the monkey central nervous system. The Journal of comparative neurology, ,377 (3 ),365-80

MacLennan, A J; Vinson, E N; Marks, L; McLaurin, D L; Pfeifer, M; Lee, N (1996. )Immunohistochemical localization of ciliary neurotrophic factor receptor alpha expression in the rat nervous system. The Journal of neuroscience : the official journal of the Society for Neuroscience, ,16 (2 ),621-30

MacLennan, A J; Gaskin, A A; Vinson, E N; Martinez, L C (1996. )Ciliary neurotrophic factor receptor alpha mRNA in NB41A3 neuroblastoma cells: regulation by cAMP. European journal of pharmacology, ,295 (1 ),103-8

MacLennan, A J; Lee, N; Walker, D W (1995. )Chronic ethanol administration decreases brain-derived neurotrophic factor gene expression in the rat hippocampus. Neuroscience letters, ,197 (2 ),105-8

Lado, D C; Browe, C S; Gaskin, A A; Borden, J M; MacLennan, A J (1994. )Cloning of the rat edg-1 immediate-early gene: expression pattern suggests diverse functions. Gene, ,149 (2 ),331-6

MacLennan, A J; Lee, N; Vincent, S R; Walker, D W (1994. )D2 dopamine receptor mRNA distribution in cholinergic and somatostatinergic cells of the rat caudate-putamen and nucleus accumbens. Neuroscience letters, ,180 (2 ),214-8

MacLennan, A J; Gaskin, A A; Lado, D C (1994. )CNTF receptor alpha mRNA expression in rodent cell lines and developing rat. Brain research. Molecular brain research, ,25 (3-4 ),251-6

MacLennan, A J; Browe, C S; Gaskin, A A; Lado, D C; Shaw, G (1994. )Cloning and characterization of a putative G-protein coupled receptor potentially involved in development.Molecular and cellular neurosciences, ,5 (3 ),201-9

Maclennan, A J; Shaw, G (1993. )A yeast SH2 domain. Trends in biochemical sciences, ,18 (12 ),464-5

Tobin, A J; Brecha, N; Chiang, M Y; Endo, S; Erlander, M G; Feldblum, S; Houser, C R; Kaufman, D L; Khrestchatistky, M; MacLennan, A J (1992. )Alternative forms of GAD and GABAA receptors. Advances in biochemical psychopharmacology, ,47 ,55-66

Khrestchatisky, M; MacLennan, A J; Tillakaratne, N J; Chiang, M Y; Tobin, A J (1991. )Sequence and regional distribution of the mRNA encoding the alpha 2 polypeptide of rat gamma-aminobutyric acidA receptors. Journal of neurochemistry, ,56 (5 ),1717-22

Tobin, A J; Khrestchatisky, M; MacLennan, A J; Chiang, M Y; Tillakaratne, N J; Xu, W T; Jackson, M B; Brecha, N; Sternini, C; Olsen, R W (1991. )Structural, developmental and functional heterogeneity of rat GABAA receptors. Advances in experimental medicine and biology, ,287 ,365-74

MacLennan, A J; Brecha, N; Khrestchatisky, M; Sternini, C; Tillakaratne, N J; Chiang, M Y; Anderson, K; Lai, M; Tobin, A J (1991. )Independent cellular and ontogenetic expression of mRNAs encoding three alpha polypeptides of the rat GABAA receptor. Neuroscience, ,43 (2-3 ),369-80

Radke, J M; MacLennan, A J; Beinfeld, M C; Bissette, G; Nemeroff, C B; Vincent, S R; Fibiger, H C (1989. )Effects of short- and long-term haloperidol administration and withdrawal on regional brain cholecystokinin and neurotensin concentrations in the rat. Brain research, ,480 (1-2 ),178-83

MacLennan, A J; Pelleymounter, M A; Atmadja, S; Jakubovic, A; Maier, S F; Fibiger, H C (1989. )D2 dopamine receptors in the rat prefrontal cortex: characterization and alteration by stress. Brain research, ,477 (1-2 ),300-7

Radke, J M; MacLennan, A J; Vincent, S R; Fibiger, H C (1988. )Comparison between short- and long-term haloperidol administration on somatostatin and substance P concentrations in the rat brain. Brain research, ,445 (1 ),55-60

MacLennan, A J; Atmadja, S; Lee, N; Fibiger, H C (1988. )Chronic haloperidol administration increases the density of D2 dopamine receptors in the medial prefrontal cortex of the rat. Psychopharmacology, ,95 (2 ),255-7

MacLennan, A J; Maier, S F (1983. )Coping and the stress-induced potentiation of stimulant stereotypy in the rat. Science (New York, N.Y.), ,219 (4588 ),1091-3

MacLennan, A J; Drugan, R C; Maier, S F (1983. )Long-term stress-induced analgesia blocked by scopolamine. Psychopharmacology, ,80 (3 ),267-8

MacLennan, A J; Drugan, R C; Hyson, R L; Maier, S F; Madden, J; Barchas, J D (1982. )Dissociation of long-term analgesia and the shuttle box escape deficit caused by inescapable shock. Journal of comparative and physiological psychology, ,96 (6 ),904-12

MacLennan, A J; Drugan, R C; Hyson, R L; Maier, S F; Madden, J; Barchas, J D (1982. )Corticosterone: a critical factor in an opioid form of stress-induced analgesia. Science (New York, N.Y.), ,215 (4539 ),1530-2

Beninger, R J; MacLennan, A J; Pinel, J P (1980. )The use of conditioned defensive burying to test the effects of pimozide on associative learning. Pharmacology, biochemistry, and behavior, ,12 (3 ),445-8

Wilkie, D M; MacLennan, A J; Pinel, J P (1979. )Rat defensive behavior: burying noxious food.Journal of the experimental analysis of behavior, ,31 (3 ),299-306

Muthuvel Arumugam, Richard Ahrens, Heather Osterfeld, Leah C. Kottyan, Xun Shang, A. John Maclennan, Nives Zimmermann, Yi Zheng PhD, Fred. D. Finkelman, Simon P. Hogan Increased Susceptibility of 129SvEvBrd mice to IgE-Mast cell mediated anaphylaxis .

The three papers described in section 8 .

Student Advising

Zhenglei Pei (Other )Committee Member

Margaret Wood (Other )Committee Member

Chang Xiao (Other )

Rob Littleton (Other )

Heather Chapman (Other )

Rachel Spearry (Undergrad )

Jordan Woods (Undergrad )

Jordan Woods (Undergrad )

Kendra Leahy (Undergrad )

Zirong Gu (Other )Committee Member

Service

(Distance Learning Committee )Member Type:Departmental Service Level:Department

Systems Biology and Physiology Graduate Program (Signal Transduction Systems Group )Other Type:Departmental Service Level:Department

(Recruitment and Admissions Committee )Member Type:Departmental Service Level:Department

Medical Research Council (England) (NC3Rs Research Grant Applications )Reviewer Type:Editorial Service Level:International 04-2010

Professional Affiliation

(This should be in the form of a self-evaluation and should take into account the departmental workload document.) We haven’t published anything so far this year but the lymphoma paper finally looks like it will be accepted (may be by the time we meet). It has taken a long time to get it published primarily because we have insisted on trying to get what we consider a particularly important result into a high impact journal. To review, our S1P2 receptor knockout mice develop a lethal form of lymphoma very prevalent in humans but rare in mouse models. Unlike other models the cancer is found in a high percentage of the mice, remarkably restricted to the one specific cancer and found only with aging (as in humans). In addition, our collaborators have found that approximately 25% of the corresponding tumors in humans contain mutations in the S1P2 gene, suggesting that such mutations in this newly discovered tumor suppressor may substantially contribute to the human disease. Perhaps understandably, the reviewers during this saga have kept sending us back to collect more data regarding the cellular mechanisms underlying the effect. The paper will not likely help my career as much as the neuroscience papers more closely related to my field of expertise and funding. However, it is ironic that by the end of my career I think it is quite possible that it will be the paper with the biggest general impact. After getting the stem cell grant application out in October we focused back on the neuromuscular project, while also working to complete the first stem cell paper. At the present pace, I expect to write 2-3 major papers this year which will each report the results of projects that have taken 5+ years to accomplish. Hopefully, we will be able to publish them in high impact journals and use them as a foundation for future funding. In this regard, recent preliminary data suggests we have finally found the cellular mechanism responsible for the reduced motor recovery following nerve lesion that we observe in our muscle specific CNTF receptor knockout mice. It looks like it’s a surprising decrease in sensory axon regeneration while motor axons are apparently unaffected. If this holds up, it will not only make it an interesting neuroscience (not just muscle) story, which as discussed above, is good for my career, it will also nicely complete the paper and suggest further (hopefully fundable) neuroscience studies. As I reported last year, we find that when CNTF receptor signaling is disrupted in vivo in a subset of adult motor neurons, through use of estrogen receptor-Cre inducible gene disruption, the neurons survive even if their axons are cut. This year we found that is also true if the region containing the motor neuron cell bodies is traumatically insulted. However, these experiments don’t tell us whether the receptor plays a role in maintaining or regenerating motor neuron axons because the reporter used labels the soma only. Using a new reporter that fills the complete motor neuron and its processes with YFP upon Cre activation, we have recently collected preliminary data that suggests that the receptor plays a major role in maintaining the axons. If it holds up, the result would be very important because recent work with ALS models suggest that the symptoms and lethal aspects of this highly prevalent motor neuron disease are the result of axonal dieback and not the loss of cell bodies. I admit I have yet to decide how these results (and potentially the muscle knockout results described above) are best used in a renewal application for the neuromuscular project but it is most likely that they will be the central findings we propose to build upon. We have also continued our UC collaborations with Drs. Simon Hogan (S1P2 receptors and gut-based anaphylaxis), Randy Seeley (CNTF receptors and weight regulation), and Jeff Molkentin (CNTF receptors and cardiovascular function).

Courses Taught

Contact Information

Medical Sciences Building
Room 4200
Cincinnati  Ohio, 45267-0576
Phone: 513-558-0667
Fax: 513-558-5738
maclenaj@ucmail.uc.edu